This paper concentrates on the general birth-death processes with two different types of catastrophes. The Laplace transform of transition probability function for birth-death processes with two-type catastrophes are is successfully expressed with the Laplace transform of transition probability function of the birth-death processes without catastrophe. The first effective catastrophe occurrence time is considered. The Laplace transform of its probability density function, expectation and variance are obtained.

This study investigated the trends of registered Death and Birth in Nigeria using Generalized Linear Models. Annual data on Death and Birth was collected from National Population Commission for the period of 2004 to 2017. The Natural increase calculated revealed a positive trend in the natural increase in Nigeria from 2004 to 2017. Evidence from summary statistics revealed some level of over dispersion (variance > mean). This study explored Poisson Regression Models and Negative Binomial Regression Models using two links (identity and log). The results revealed a positive increase in registration of birth and death rates in Nigeria and among the competing the models, Negative Binomial regression model with identity link emerged as the best model for modeling birth and death rates registration in Nigeria. Data on numbers of deaths and causes of death are essential if countries are to determine priorities, formulate and monitor policies for public health care as well as other government policies that may be based on such data

Objective: To determine the effect of birth season climate on adult total serum IgE (TSIgE) levels. Study design: The study is a retrospective chart review with the following inclusion criteria: TSIgE measurement, age ≥16, and northeastern Tennessee birthplace. Main outcome measures include TSIgE levels, birth season climatic conditions, and regional pollen-producing plant and pollen counts. Results: The records of 1,274 women (mean age 40.8 ± 17.5, age range 16-96) and 762 men (mean age 38.1 ± 17, age range 16-82) seen in our Allergy Clinic were reviewed. Persons born in the spring and summer, the seasons with the highest pollen counts and the most favorable climatic conditions for plant growth, had nearly twice the odds of having TSIgE levels >1σ above the mean of the study group when compared to those born in the fall or winter (odds ratio (OR) 1.75, 95% confidence interval (CI) 0.96-3.17 and OR 1.93, 95% CI 1.04-3.57, respectively); odds were highest for those born in March (OR 2.55, 95% CI 1.37-4.74) and July (OR 2.38, 95% CI 1.25-4.51) and lowest for those born in November (OR 0.11, 95% CI 0.0068-1.79). When averaged over the 95-years of study and five 30-year climate cycles TSIgE levels increased linearly as the seasons progressed from fall to summer (r²= 0.9475, P=0.0266). Of the climatic factors, TSIgE levels correlated most strongly with levels of precipitation (r²= 0.9145, P=0.0437). Conclusion: Climatic conditions that increase birth season exposure to environmental allergens may have a life-long effect on TSIgE production.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in the offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that MBW of <2,500 g (low MBW) was associated with increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while MBW of ≥4,000 g (high MBW) with congenital anomalies of the urinary tract (2.194, [1.261–3.819]), and arrhythmia (1.775, [1.157–2.725]), compared with those with MBW of 3,000-3,499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs(1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease(1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circum-stances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, we selected mechanisms by which viruses interfere with cell death are discussed in-depth and are used to illustrate the general principles and cellular signaling mechanisms of virus-host specific molecule interactions.

Findings from studies of prenatal exposure to pesticides and adverse birth outcomes have been equivocal so far. We examined prenatal exposure to agricultural pesticides in relation to preterm birth and term low birthweight, respectively, in children born between 1998 and 2010 randomly selected from California birth records. We estimated residential exposures to agriculturally applied pesticides within 2 km of residential addresses at birth by pregnancy trimester for 17 individual pesticides and 3 chemical classes (organophosphates, pyrethroids, and carbamates). Among maternal addresses located within 2 km of any agricultural pesticide application, we identified 24,693 preterm and 220,297 term births, and 4,412 term low birthweight and 194,732 term normal birthweight infants. First or second trimester exposures to individual pesticides (e.g., glyphosates, paraquat, imidacloprid) or exposures to 2+ pesticides in the three chemical classes were associated with small increases (3-7%) in risk for preterm birth; associations were stronger for female offspring. We did not find associations between term low birthweight and exposures to pesticides other than for myclobutanil (OR: 1.11; 95% CI: 1.04-1.20) and possibly pyrethroids as a class. Our improved exposure assessment revealed that first and second trimester exposures to pesticides were associated with preterm delivery but few affected term low birthweight.

Lewis et al. published an important and timely necessary article about the determination of death by neurological criteria, revising the Uniform Determination of Death.The acceptance of brain death (BD) has been progressively accepted beginning at the late 1950s. Nonetheless, contentious brain-death cases have recently raised new controversies about the diagnosis of BD, such as the Jahi McMath case, extensively covered by the US and international press. Jahi McMath meant a terrible tragedy for her and her family. But further than this gloomy story, the case has also raised confusion and challenging qualms about a fundamental query: how we confirm whether a person is dead or alive? Since 1981, the Uniform Determination of Death Act (UDDA) has served as the legal foundation for the medical practice of determining death. But, although death by neurologic criteria is considered legal death throughout the United States, several recent lawsuits have quizzed the rightfulness the authority of the UDDA to declare death by neurological criteria. This issue explains the importance of Lewis’s et al. paper. In this article I want to present the historical procedure for issuing a law in Cuba for the determination and certification of death. Of course, it is impossible to compare our country with USA. Cuba is a small and developing country, in which a law encompasses a national scenery, in contrast with USA, a multistate nation.

Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.

This research article provides a comprehensive analysis of the Expectation of Life at Birth in India and its larger states and union territories (UTs), with a specific focus on rural and urban disparities. The data, obtained from the Ministry of Health and Family Welfare of India, highlights the variations in life expectancy by sex and area of residence, shedding light on the health and socio-economic conditions in different regions. The article discusses the implications of these findings and their relevance for public health policy and interventions.

Fertilized zygotes normally display 2 pronuclei (PN) but abnormal fertilization patterns (0, 1 or >2 PN) are daily observed in IVF labs. Multiple PN zygotes (>2) are generally discarded due to an increased risk of aneuploidy. However, the decision to transfer or not 1PN-derived embryos remains controversial. The aims of our study were to analyze the neonatal outcomes of fresh or frozen-thawed embryos derived from 1PN zygotes, and to evaluate the influence of the fertilization method. Data were retrospectively collected from cycles performed between January 2018 and December 2022. Fresh cycles were analyzed for the comparative fate of 1PN zygotes (n=1234) following conventional in vitro fertilization (cIVF; n=648) or intracytoplasmic sperm injection (ICSI; n=586), as well as the results of the 64 transfers of 1PN derived embryos (pregnancy rate (PR) and neonatal outcomes). This pregnancy follow-up was also applied to 167 transfers of frozen-thawed 1PN derived embryos. In fresh cycles, 46% of the 1PN zygotes in cIVF group gave rise to embryos of sufficient quality to be transferred or frozen (day 3 or 5/6). This rate decreased to 33% in the fresh ICSI cycles. Blastulation rate was also significantly higher in cIVF group (44%) in comparison to ICSI group (20%). The fresh embryo transfers (32 per group) allowed 7 pregnancies in the cIVF group (PR=21.9%) as compared to 4 pregnancies in the ICSI group (PR=12.5%). In the cIVF group, 4 deliveries of healthy newborns were achieved and only one in the ICSI group. In frozen/thawed cycles, 36 pregnancies were obtained out of the 167 transfers. A non-significative difference was observed between embryos derived from cIVF cycles (PR=26%) and ICSI cycles (PR=16%) with respectively 18 and 8 healthy babies born. In conclusion, we observed better outcomes for 1PN zygotes in cIVF cycles in comparison to ICSI cycles. Our center policy to transfer good quality 1PN-derived embryos allowed the birth of 31 healthy babies.

Background: Despite tremendous efforts to reduce neonatal mortality worldwide and in 24 Ethiopia, there is the country is one of the countries with highest neonatal morbidity and health 25 losses. Never the less, the past three decades’ national trend and subnational distribution of 26 neonatal morbidity and mortality and its health loss in Ethiopia, was not well documented. 27 Hence, this study had aimed to analyze the trend and distributions as well as health losses 28 resulting from neonatal morbidity in the past three decades in Ethiopia, 2019. 29 Objective: To assess the national trend and sub national distributions of neonatal morbidity and 30 neonatal mortality in the previous three decades by using Global Burden of Diseases, 2019 data. 31 Methods: The data sources were primary and secondary data related to risk factors, morbidity, 32 disability, deaths, Disability Adjusted Life Years, Years Lived with Disability and Years Life Lost 33 were collected form case studies and case series, household surveys, socio-demographic surveys 34 and surveillances, health facilities surveys, Health facility observations and interviews and 35 published and unpublished literatures. The prevalence, deaths and health losses were calculated 36 by using embedded model. The study period covered from 1990 to 2019. Results were presented 37 buy using texts, tables and graphs. 38 Results: Seventy percent of neonatal disorders had occurred among early neonates aged 0 to 6 39 days. Between 1990 and 2019, the national prevalence of neonatal disorders had increased by 40 47% in to 28,319 (95% UI, 25646-30,361). Bet Similarly, the highest number of neonatal deaths 41 caused by neonatal sepsis had shifted from Southern Nations Nationalities and Peoples region to 42 Oromia region while Harari remains to bear the lowest burden in the last three decades. The 43 highest and the lowest YLL as a result of neonatal disorders had occurred in Oromia 44 [(2,753,038,95% UI, 2,184,142-3,497-926) and Amhara 1,360,847 [(95% UI, 95% UI, 45 1,062,660-1,762,028)] regions respectively. Unlike other regions, Addis Ababa had the highest 46 (52%) prevalence of preterm birth in 2019 47 Conclusion and Recommendation: About seven in ten of neonatal death had occurred among 48 early neonates indicating narrowed occurrence of the event. The highest and the lowest number 49 of neonatal death and health loss had occurred in Oromia and Harari regions respectively. The 50 main causes of death were neonatal sepsis and other infections, neonatal preterm, hemolytic 51 disease and other jaundice and neonatal encephalopathy and trauma. Hence, Contextualized, 52 locally accepted innovative early neonatal care is crucial to avert the event.

The increasing number of caesarean section (CS) is a major challenge in modern obstetrics. This rise is not supported by better neonatal and maternal outcomes. The prevention of unnecessary primary CS is a global priority. This study focuses on effectiveness and safety of yoga practice during pregnancy and it’s connection to perinatal outcome. We conducted a single-blinded, randomized controlled clinical trial, with healthy singleton primiparas, randomized at first trimester of pregnancy. A total of 214 participants were randomized, 106 in yoga and 108 in controls. The study group performed yoga exercise while the controls received standard antenatal care. The yoga exercises were performed once a week, lasted 90 minutes, under the supervision of a certified yoga teacher. All pregnant women from study group completed 12 yoga exercises. The results showed that the yoga group had a lower rate of urgent intrapartum CS (p-0.004) and more frequent spontaneous vaginal delivery (p-0.009), while the control group had a higher rate of induced labour (p-0.032). Conclusion: Yoga practice in pregnancy is a promising intervention that has a potential to decrease intrapartum urgent CS rates and assures natural and spontaneous vaginal birth; it’s highly recommendable to healthy pregnant women.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides’ fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest methods to analyze the lipids in biological samples. Finally, we discuss the drug development strategies focusing on the ceramide synthases and ceramides as future therapeutic approaches in cancer therapy.

Cell death resistance is a key feature of tumor cells. One of the main anti-cancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

Background and objectives: The impact of prenatal exposure to polycyclicaromatic 17 hydrocarbons (PAHs) on birth outcomes as weight, length, head circumference, placenta 18 weight, and Apgar. Materials and Methods: Two cohorts of children born in the years 2013 and 19 2014 in Karvina (Northern Moravia, N=144) and Ceske Budejovice (Southern Bohemia, 20 N=198), were studied for the relationship between the prenatal exposure to PAHs and growth 21 parameters up to two years of age. PAHs exposure was evaluated according to the concentration 22 of benzo[a]pyrene (B[a]P) in polluted air and monohydroxylated PAH metabolites (OH-PAHs) 23 in urine of newborns as well as their mothers. Data of growth parameters were obtained from 24 pediatric questionnaires up to 24 months. 25 Results: Concentrations of B[a]P were significantly higher in Karvina (p<0.001). OH-26 PAH metabolites were significantly higher in the mothers´ as well as in the newborns´ urine in 27 Karvina. The length was shorter in newborns in Karvina at birth (p<0.001), but this difference 28 was straightened out during next 3 to 24 months. Birth weight at the delivery did not differ 29 between newborns in Karvina and Ceske Budejovice. Newborns in both locations significantly 30 decreased their weight gain between birth and 3 months after delivery. OH-PAHs metabolites 31 in mother’s or newborn’s urine did not affect birth weight. Top 25% values of concentrations 32 of 2-OH-FLUO, 1-OH-NAP, 2-OH-NAP, 1-OH-PHEN, 2-OH-PHEN, 3-OH-PHEN, 4-OH-33 PHEN, and the sum of all-OH-PAHs higher than median in the newborns´ urine decreased their 34 length. 2-OH-PHEN top 25% of concentrations in the newborns´ urine decreased their head 35 circumference, 2-OH-FLUO, 1-OH-NAP, 2-OH-NAP, 1-OH-PHEN, 2-OH-PHEN, 3-OH-36 PHEN, 4-OH-PHEN, 9-OH-PHEN, 1-OH-PYR, and all-OH-PAHs decreased placenta weight; 37 2-OH-FLUO, 1-OH-NAP, 2-OH-NAP, 1-OH-PHEN, 2-OH-PHEN, 3-OH-PHEN, 4-OH-38 PHEN, and all-OH-PAHs decreased Apgar 5´. Conclusions: We observed that higher 39 concentration of PAHs determined as OH-PAHs metabolites in newborns´ urine decreased their 40 length, head circumference, placenta weight, and Apgar 5´, but did not affect birth weight.

Sudden unexpected death (SUD) is a fatal event that occurs in an apparently healthy subject so that such an abrupt outcome could have not been predicted. SUD - including sudden intrauterine unexplained death (SIUD), sudden neonatal unexpected death (SNUD), sudden infant death syndrome (SIDS), sudden unexpected death of the young (SUDY), sudden unexpected death in the adult (SUDA) - occurs as the first manifestation of an unknown underlying disease or within a few hours of presentation of a disease. SUD is a major unsolved, shocking form of death that occurs frequently and can happen at any time without warning. For each case of SUD, a review of clinical history data and performance of a complete autopsy, particularly focused on the study of the cardiac conduction system were carried out according to the necropsy protocol devised by the Lino Rossi Research Center, Università degli Studi di Milano, Italy. Research cases are represented by 75 SUD victims, subdivided into 15 SIUD, 15 SNUD, 15 SUDY, and 15 SUDA victims, collected and selected for this study. After the routine autopsy and clinical history analysis, the death remained unexplained and hence a diagnosis of SUD was assigned to the 75. subjects, which included45 females (60%) and 30 (40%) males, ranging in age from 27 gestational weeks to 76 years. Serial sections of the cardiac conduction system disclosed frequent congenital alterations, of the cardiac conduction system in fetuses and infants. An age-related significant difference in distribution among the 5 age-related groups was detected for the following anomalies of the conduction system: central fibrous body (CFB) islands of conduction tissue, fetal dispersion, resorptive degeneration, Mahaim fiber, CFB cartilaginous meta-hyperplasia, His bundle septation, sino-atrial node (SAN) artery fibromuscular thickening, atrio-ventricular junction hypoplasia, intramural right bundle branch, and SAN hypoplasia. The results data are useful to understand the cause of death for all SUD cases that were unexpected and would have otherwise remained unexplained, so to motivate medical examiners and pathologists to perform more in-depth studies.

Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: To discuss the particularities of diagnosis BD in patients with posterior fossa lesions. Material and Methods. The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions [i.e., cerebral hypoxia], the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions [i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum] may retain intracranial blood flow and EEG activity. In this article I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also address Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.

Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause Placental Schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any sys-tematic review on PS. Methods: We conducted a systematic literature search on PubMed and in-cluded relevant secondary literature found in the citations of the primarily included publications. Results: We found a total of 8 publications describing PS with a total of 92 cases, describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association to adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only < 1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in en-demic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. These data were used to calculate cervical elasticity, as a stress-to-strain ratio. CM examination data were analyzed for 127 women at 24 - 28 gestational weeks. PTB was observed in 6.3% (8 out of 127) of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70±0.26 kPa/mm compared to the term group's 1.63±0.65 kPa/mm, with a significant p-value of 1.1×10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5–100.0). These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe could potentially predict spontaneous preterm birth in a cost-effective manner.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is important for treatment planning and managing patient expectation, particularly in their first in vitro fertilization (IVF) cycle. Cryopreservation of supernumerary embryos is often regarded as an important prognostic variable and a surrogate marker of success for several reasons. While previous large studies have examined the association between the number of oocytes retrieved and cleavage-stage embryos available, and the odds of a live birth following a fresh embryo transfer, the relationship between the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis of data collected between 2006 and 2018 for all first time IVF patients with a fresh autologous day 5 single blastocyst transfer. The relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved was assessed according to patient age group. In patients aged <35 years and 35-39 years old, the likelihood of a live birth increased linearly from 0.33 (95%CI:0.31–0.34) to 0.80 (95%CI:0.74–0.86; P<.0001) and 0.30 (95%CI:0.28–0.32) to 0.82 (95%CI:0.73–0.91;P<.0001) between 1-6 blastocysts cryopreserved and then non-linearly to 0.95 (95% CI 0.92–0.97; P<.0001) and 0.96 (95%CI:0.93–0.99; P<.0001) if 10 or more blastocysts were cryopreserved, respectively. When aged 40 years and above, the likelihood of a live birth increased linearly from 0.26 (95%CI:0.19–0.32) to 0.83 (95%CI:0.68–0.97; P<.0001) between 1-4 blastocysts cryopreserved and then non-linearly to 0.99 (95%CI:0.98–0.99; P<.0001) if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts have been funded in Italy as the first step to diagnosing individuals unaware of their infection. The aim of this study is to use available in-hospital routine screening data to understand the inpatients HCV screening in a region of North Italy. A retrospective search of in-hospital patients tested for HCV-antibody (HCV-Ab) from January 2017 to the end of December 2022, was conducted according to age categories (older than 76 years, birth group 1947-1968; birth group1969-1989 and two other categories with patients younger than 33 years) using the TriNetX network. Of 42,805 in-hospital patients tested, 1,297 (3.03%) resulted HCV-Ab positive. The proportion decreased from 2017 to 2022 (from 2.03% to 0.36%) years). The higher prevalence of HCV-Ab was in patients older than 76 years (5.3%) while, the lowest was in the younger birth cohort (2000-2022, 0.16%). Of 1,297 patients found HCV-Ab positive, only 198 (15.3%) were tested for the presence of HCV RNA. Although the birth cohort 1969-1989 had a lower seroprevalence (1.5%), they represented the most affected age group with 44.4% of HCV RNA positivity. The in-hospital HCV screening including birth cohort 1947-1989 could be a valuable option respect to the screening for birth group 1969-1989 in the general population. Since a high proportion of patients were not tested for HCV RNA during hospitalization, reflex testing promptly ascertaining an active infection could facilitate linkage to care to stop the burden of HCV.

Dermal pigmentation is a challenging condition due to relative resistance to medical treatment and requirement of multiple sessions with modalities like chemical peels and lasers. There is inadequate literature regarding the efficacy and safety of lasers for dermal pigmentation in Indian skin. One hundred and twenty two patients were enrolled and divided into 4 groups: a) Dermal melasma b) Acquired dermal macular hyperpigmentation c) Nevus and d) Tattoo. Sequential combination of various lasers were used with different protocols for 4 different groups like ablative pixel Er:YAG, intense pulse light based technologies, Q-Switched and Alma Hybrid lasers for treatment of dermal pigmentation. A total of 4-10 sessions were conducted at three weekly intervals. Results were evaluated by comparing photographs at baseline, one month after the last session and then at 6 months interval to assess the relapse. All groups showed a statistically significant reduction in pigmentation. The mean treatment duration was 5-7 months for tattoo, lichen planus pigmentosus and melasma with 6-8 number of sessions. The mean treatment duration for nevus was 7-9 months with 8-10 sessions. Lasers are safe and effective modalities in Indian skin type for treatment of dermal pigmentation. Treatment period and relapse of dermal pigmentation may be reduced by combining resurfacing and chromophore selective lasers along with adequate dietary and lifestyle modifications to minimize complications and recurrence rates.

(1) Background: This study aimed to evaluate the role of cervical pessary for preventing preterm birth in singleton pregnant women with a cervical length (CL) ≤25 mm and a uterocervical angle (UCA) ≥95o and ≥105o. (2) Methods: A quasi-experimental study was conducted on 225 singleton pregnant women with a gestational age of 16+o-23+6 weeks and transvaginal ultrasound CL measurements ≤25 mm, whose pregnancy was man-aged at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, from September 2020 to September 2022. Participants were allocated into two groups: prophylactic treatment with progesterone (123 pregnant women) and combined with a cervical pessary (102 pregnant women). The UCAs measured via transvaginal ultrasound by a single sonographer were divided into groups with UCA measurements ≥95o and ≥105o. The gestational age at birth was classified into full-term and preterm <37 weeks and <34 weeks. A binary regression model assessed the association between CL, UCA, and pre-term birth outcomes. The difference was statistically significant, with p<0.05. (3) Results: There was no statistically significant difference in the rate of preterm birth <37 weeks and <34 weeks between the two groups (16.3% vs. 11.8% and 6.5% vs. 4.9%, p>0.05). The probability of preterm birth <37 weeks in the group of pregnant women with a UCA ≥95o treated via cervical pessary plus progesterone decreased by 60.6%, OR (95% CI) of 0.394 (0.165-0.941), p<0.05. In the group of pregnant women with a UCA ≥105o, there was a significant association in the group of progesterone treatment combined with a cervical pessary, with the lower rate of PTB <37 weeks and <34 weeks, with OR (95% CI) of 0.028 (0.005-0.146), p<0.001, and 0.141 (0.030-0.664), p<0.05, respectively. (4) Conclusion: The results of this study suggest that cervical pessary is beneficial to the prevention of preterm birth in singleton pregnant women with an obtuse uterocervical angle. Further randomized studies among pregnant women with obtuse uterocervical angles will be needed to clarify the role of a cervical pessary in preventing preterm birth.

AbstractPurpose: This study aimed to perform a psychometric evaluation of the preliminary preterm birth risk assessment scale (PBRAS-K) of 32-item. Method(s): There were 299 subjects, 167 in the exploratory factor analysis (EFA) group and 132 in the confirmatory factor analysis (CFA) group, who delivered before 37⁺⁰ weeks after having preterm symptoms and were admitted to high-risk pregnancy maternal-fetal intensive care units (MFICU). After an item reduction process in EFA, the psychometric property scales were assessed using SPSS 26, and CFA was accomplished using AMOS 27. Results: The Kaiser-Meyer-Olkin measure (KMO) and Bartlett’s χ² test of sphericity confirmed the adequacy of the sample for factor analysis (KMO = .81 (> .80), χ² = 1841.38, p < .001). The final version of the PBRAS-K was comprised of 23 items within seven dimensions. Factor analysis identified items explaining 65.9% of the total variance. The PBRAS-K had a mean score of 35.58 (±10.35) and showed a high internal consistency and satisfactory reliability with a Cronbach’s alpha of .85. The PBRAS-K had a low correlation with risk scoring of preterm delivery (RPD) for discriminant validity (r = .45, p < .001), a positive, high correlation with the Somatic Awareness Scale with Spontaneous Preterm Labor (SPL-SAS) for criterion validity (r = .65, p < .001), and with pregnant stress for convergent validity (r = .57, p < .001). RPD and SPL-SAS were moderately correlated (r = .53, p < .001). Conclusion(s): The PBRAS-23-K is a valid and reliable instrument for assessing pregnant women’s risk of preterm birth. Clinical nurses are encouraged to apply and obtain information for effective interventions in MFICU. This scale has meaningful results and reflects the voices of women who had a preterm birth. The scale should be evaluated for standardization and cut-off scores using larger subject sizes in the future.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

Introduction: Intrauterine fetal death (IFD) is death of fetus after the 20th week of gestation. Despite regular monitoring, the incidence of IFD remains high. This study aims to assess the incidence and risk factors for IFD in term pregnancies for better prevention and reduction of neonatal morbidity and mortality. Materials and Methods: A retrospective cohort study was conducted with term pregnant women diagnosed with IFD. The analysis included the number of deliveries, live births, and stillbirths. Statistical analysis involves descriptive and analytical statistical methods. Results: Average age was 30 years. Most patients had intermediate and high education, and one-third of patients had regular pregnancy monitoring. 53.33% were primiparous, and pregnancies occurred spontaneously. IFD mainly occurred in the 39th week of gestation. The average birth weight was approximately 3000g. 38.3% had one to two associated diseases, 5% more than three, and 56.7% were healthy. Recurrence of IFD was reported by 10% of patients, while 8.33% had a history of spontaneous abortion. Over 80% of placental histopathological findings indicated some pathology (infarction, infections, abruptio placenta). Conclusion: The most significant risk factors were pregnancy-induced hypertensive disorders, obesity, and diabetes, followed by hypothyroidism, maternal tachycardia, and anemia.

Retinitis pigmentosa (RP) is a frequent cause of blindness among the working population in industrial countries, due to the inheritable death of photoreceptors. Though a gene therapy was recently approved for mutations in the RPE65 gene, there is generally no effective treatment presently. Previously, abnormally high-level cGMP and overactivation of its dependent protein kinase (PKG) have been suggested as causative for the fatal effects on photoreceptors, making it meaningful to explore the cGMP-PKG downstream signaling for more pathological insights and novel therapeutic target development purposes. Here we manipulated the cGMP-PKG system in degenerating retinas from the rd1 mouse model pharmacologically via adding a PKG inhibitory cGMP-analogue to organotypic retinal explant cultures. A combination of phosphorylated peptides enrichment and mass spectrometry was then applied to study the cGMP-PKG-dependent phosphoproteomics. We identified a host of novel potential cGMP-PKG downstream substrates and related kinases using this approach, and selected the RAF1 protein, which may act as both a substrate and a kinase, for further validation. We showed that the RAS/RAF1/MAPK/ERK pathway may be involved in retinal degeneration in a yet unclarified mechanism, thus deserving further investigation in the future.

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

Necroptosis is an inflammatory form of lytic programmed cell death that is thought to have evolved to defend against pathogens. Genetic deletion of the terminal effector protein – MLKL – shows no overt phenotype in the C57BL/6 mouse strain under conventional laboratory housing conditions. Small molecules that inhibit necroptosis by targeting the kinase activity of RIPK1, one of the main upstream conduits to MLKL activation, have shown promise in several murine models of non-infectious disease and in phase II human clinical trials. This has triggered multi-billion-dollar investments into the emerging class of necroptosis blocking drugs, and the potential utility of targeting the terminal effector is being closely scrutinised. Here we review murine models of disease, both genetic deletion and mutation, that investigate the role of MLKL. We summarize a series of examples from several broad disease categories including ischemia reperfusion injury, sterile inflammation, pathogen infection and haematological stress. Elucidating MLKL’s contribution to mouse models of disease is an important first step to identify human indications that stand to benefit most from MLKL-targeted drug therapies.

Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.

The decline in assisted reproductive technology (ART) success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus ex-ists on the optimal ovarian stimulation protocol for older women undergoing IVF. This retrospec-tive registered cohort study aimed to compare cumulative live birth rates (CLBR), time to live birth (TTLB), and cost-effectiveness in women over 35 years using gonadotropin-releasing hor-mone agonist (GnRHa) or clomiphene-primed ovarian stimulation (CPOS). We performed pro-pensity score matching (PSM) on 2,871 IVF cycles in women over 35 who received either GnRHa or CPOS protocols, resulting in 375 cycles in each group to compare treatment outcomes. Addition-ally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Fol-lowing PSM, both groups showed similar baseline characteristics. The CPOS protocol exhibited a higher cycle cancellation rate (13.07% vs 8.00%, p=0.032), yet maintained comparable fertilization and embryo quality. While CLBRs per initial cycle (41.07% vs. 45.33%, p=0.269) and delivery out-comes were similar between the groups after a 24-month follow-up, TTLB was longer in the CPOS group. Notably, the average cost per live birth in the CPOS group was 21.27% less than that in the GnRHa group (￥32,301.42 vs ￥39,174.22). In conclusion, for women over 35 undergoing IVF, the CPOS protocol demonstrated similar CLBR to GnRHa but with lower costs, suggesting its potential as a viable and cost-efficient ovarian stimulation option.

(1) Background: This study aimed to evaluate whether the implementation of a modified blood sampling protocol, which focused on need-based laboratory testing and minimized venous sampling by replacing it with point-of-care testing (POCT) via capillary puncture, successfully reduced iatrogenic blood loss, incidence of anemia, and frequency of blood transfusion in extremely low birth weight infants (ELBWIs) without negatively affecting neonatal outcomes. (2) Methods: A retrospective analysis was conducted on 313 ELBWIs of gestational age (GA) between 23 and 28 weeks, born between 2013 and 2019. The infants were divided into two groups: before (period I) and after (period II) the implementation of the modified blood sampling protocol in January 2016. Propensity score matching was conducted to minimize selection bias. Clinical data, including the frequency and amount of blood sampling, frequency and volume of blood transfusion, and clinical characteristics, such as gestational age, birth weight, and neonatal outcome data, were collected and compared between the two groups. (3) Results: No significant differences in the GA or birth weight between the two periods were observed. The total sampling volume during a month after birth (16.7 ± 4.1 mL vs. 15.6 ± 4.4 mL, P=0.03) and total sampling volume during hospital days (51.4 ± 29.7 mL vs. 44.3 ± 27.5 mL, P=0.04) in period II were significantly lower than that in period I. There were no differences in the mortality or morbidity between the two periods. Although the transfusion frequency and amount did not have significant differences between the periods, we observed a positive correlation between the transfusion frequency and sampling volume (coefficient: 0.09, 95% CI: 0.08–0.11). (4) Conclusions: The modified blood sampling protocol effectively reduced the iatrogenic blood loss without negatively affecting the neonatal outcomes.

The use of selective pro resolving mediators including the monohydroxylates are promising substances for the management of different acute and chronic diseases.In the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre-eclampsia are still serious complications during pregnancy.The use of enriched marine oil nutritional’s may contribute to an attenuation of these diseases as the containing selective pro resolving mediators exhibit pro resolutive actions that can positively modulate inflammatory diseases and those leading to serious obstetrical complications.

Introduction: Leptin is a polypeptide hormone and in pregnancy it is secreted by the placenta and maternal and fetal adipose tissues. The expression of leptin and its specific receptors is observed in the uterine endometrium which indicates leptin involvement in the implantation process and embryonic/fetal development. Normal leptin production is a factor responsible for uncomplicated gestation, embryo development and fetal growth. Objective: To compare at delivery maternal serum and cord blood leptin concentrations in normal pregnancies and in pregnancies complicated by intrauterine growth restriction (IUGR). Material and methods: The study was performed in 25 pregnant women with isolated IUGR diagnosed by ultrasonography (study subjects) and in 194 pregnant women without any comorbid health conditions (controls). Leptin concentrations in maternal serum and in cord blood samples collected at delivery were measured by ELISA and subsequently analyzed by maternal Body Mass Index (BMI), mode of delivery, and infant gender and birth weight. For comparative analyses of normally distributed variables, parametric tests were used, i.e. the Student-t to test the assumption of homogeneity or non-homogeneity of variance and a One-Way ANOVA when more than two groups were compared. The non-parametric Mann-Whitney test was used when the distribution was not normal. The Pearson correlation coefficient was calculated to assess the correlation between normally distributed variables (p<0.05). Results: In pregnancies complicated by IUGR, the mean maternal serum leptin concentration at delivery was significantly higher (52.73 ± 30.49 ng/mL) than in normal pregnancies (37.17 ± 28.07 ng/mL) (p=0.01). The mean cord blood leptin concentration in pregnancies complicated by IUGR was 7.97 ± 4.46 ng/mL and significantly lower than in normal pregnancies (14.78 ± 15.97 ng/mL) (p=0.04). In normal pregnancies, but not in pregnancies complicated by IUGR, a statistically significant correlation was established between maternal serum leptin concentrations and maternal BMI at delivery (r=0,22; p=0.00). No statistically significant correlation was found between cord blood leptin concentrations and maternal BMI in either study subjects or controls. In normal pregnancies, but not in pregnancies complicated by IUGR, a strong correlation was observed between cord blood leptin concentrations and birth weight (r=0,23; p=0.00). In both study subjects and controls, there were no correlations between leptin concentrations in maternal serum and cord blood and infant gender and mode of delivery. Conclusions: Elevated maternal blood leptin concentrations in pregnancies complicated by IUGR may indicate a significant adverse effect of elevated leptin on fetal growth. Enhanced leptin production by the placenta suggests leptin as a candidate marker of placental insufficiency. The differences in leptin concentrations, measured in maternal serum and in cord blood, between the study subjects and controls suggest that deregulated leptin levels may increase the risk of obstetric complications associated with placental insufficiency.

This randomized control trial aims to test the hypothesis that twice-daily nurse-administered saline enema(SE) is comparable to physician-administrated SE in very low birth weight infants (VLBW) with meconium obstruction of prematurity (MOP). MOP is defined as no bowel opening for 48 h, and treatment failure is defined as the need for additional intervention and safety. Twice-daily SE was administered by accredited nurses, surgeons/neonatologists using standardized protocols. The outcomes were comparability of nurse to physician-administered SE in terms of frequency of administration, catheter insertion length and volume of enema, daily maximum meconium output, and treatment failure, defined as the need for additional intervention. Safety outcomes were evaluated. Twenty-eight infants were managed with SE. 389 SE were administered, 96 and 293 in 750-999g and 1000-1500g birth weight groups, respectively. Nurses administered 72.9% and 81.5% of SE in 750-999g and 1000-1500g birth weight groups, respectively. Physicians performed the rest of the SE. Daily meconium output was comparable in nurse and physician-administered SE in both groups. There were no treatment failures or adverse events in both SE group. SE administered by nurses was found to be comparable in terms of safety, efficacy, and frequency of administration to that of physician-administered SE.

Cell death by apoptosis is a major cellular response, in the control of tissue homeostasis and as a defense mechanism in case of cellular aggression like an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the spread of a virus. Although it may contribute to the deleterious effects in infectious pathology, apoptosis remains a key mechanism for viral clearance and resolution of infection. The control mechanisms of cell death processes by viruses have been extensively studied. Apoptosis can be triggered by different viral determinants, through different pathways, as a result of virally induced cell stresses and innate immune responses. Zika virus (ZIKV) induces Zika disease in humans which has caused severe neurological forms, birth defects and microcephaly in newborns during the last epidemics. ZIKV also surprised by revealing an ability to persist in the genital tract and in semen, thus being sexually transmitted. Mechanisms of diverting antiviral responses such as the interferon response, the role of cytopathic effects and apoptosis in the etiology of the disease have been widely studied and debated. In this review, we examined the interplay between ZIKV infection of different cell types and apoptosis and how the virus deals with this cellular response. We illustrate a duality in the effects of ZIKV-controlled apoptosis, depending on whether it occurs too early or too late, respectively in neuropathogenesis, or in long-term viral persistence. We further discuss a prospective role for apoptosis in ZIKV-related therapies, and the use of ZIKV as an oncolytic agent.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review, was to investigate the association between PTB, maternal nutrition and placental-infant TL. Observational studies were sought, with the keywords: maternal nutrition, placenta TL, newborn, TL, and PTB. No study was found that included all keywords simultaneously, and thus, the keywords, were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL, is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.

The Hepatitis B virus, chronically infects over 240 million persons worldwide. The Hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 hours of life followed by a minimum of 2 subsequent doses. In October 2021, Antigua and Barbuda, through it’s only public hospital - the Sir Lester Bird Medical Centre, instituted a hospital based Hepatitis B vaccine birth dose policy. Timely birth dose coverage was 72% and total birth dose coverage 81%. 10.5% of parents refused the hepatitis b – birth dose, of which 76% either felt uncomfortable or preferred to wait. 100% of babies born before arrival received timely vaccine administration, likewise 100% of Hepatitis B exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. A maternal Hepatitis B surface antigen result was available for 90.4% of mothers. Barriers to timely birth dose administration included vaccination hesitancy, gaps in healthcare worker knowledge, and the consistent supply of Hepatitis B vaccine. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother to child transmission of hepatitis B by 2030 possible.

This study investigated mortality discrepancies in Korea, 2000-2020, with a focus on age, gender, and preventable causes of death, and their impact on life expectancy at birth. The study utilized data from Korean Standard Classification of Diseases and OECD/Eurostat lists of preventable and treatable causes of death and employed Arriaga's method. Noteworthy findings revealed gender disparities in life expectancy increases, with male gaining an advantage over females from 2000-2020 (8.142 years for males versus 6.806 years for females). The most significant increase in life expectancy was found to be in males aged 70-74 and females aged 75-79. The gender gap in LEB is narrowing and that the main age group contributing to the gender gap are getting older. Reduced gains in life expectancy at birth resulted from avoidable mortality, contributing 57.3% to the increase. Cerebrovascular disease and transport accidents were positive contributors, whereas suicide and certain cancers were negative contributors. The changes in mortality for individuals aged 65 and over had an impact of 45.44% (males) and 71.01% (females) on life expectancy gains. This study offers a novel approach in evaluating avoidable mortality and life expectancy, having the potential to improve international health indicators and inform health policies.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI &lt; 18.5 kg/m2. This study was based on observational routinely-collected data from a University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥ 12.5 kg and &lt; 12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 135 participants with a median age of 28±8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.2±45.4 vs 42.6±48.8 %; P&lt;0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (28.1% vs 11.3%; P=0.017). Our study also showed increased risks of premature rupture of membranes, anaemia and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year

Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates, however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age. The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the 1^st trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order and age at SDQ completed. The median concentrations of BPA, MnBP, MiBP, MEHP and MECPP were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. BPA level was associated with increased hyperactivity/inattention risk among girls (OR=1.66, 95% CI: 0.95-2.90) and∑DBP_m (MnBP + MiBP) level was associated with decreased total difficulties risk overall and among girls (OR=0.48, 95% CI: 0.20-1.13, OR=0.24, 95% CI: 0.06-1.03, respectively) without significance. MECPP level was associated with increase conduct problems risk (OR=2.78, 95% CI: 1.36-5.68). Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age, however, suggested possible association between MECPP levels and increased risk of conduct problems.

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has con-tinued to increase by about 1% each year in both men and women. Although the 5‐year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strate-gies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.

Phototherapy is an efficient strategy to respond to oxidative stress and has been in the spotlight in various therapeutic fields through its biological effect, but the exact molecular mechanism has not yet been established. As a result of irradiating RAW264.7 cells with a 630 nm or 850 nm LED with an energy intensity of 0.01J/cm2, cell viability was increased depend on the irradiation time. After H2O2 was added, 630 nm or 850 nm LEDs were irradiated for 10 min or 40 min to increase cell viability by about 1.7- or 1.6-fold, respectively. In addition, 630nm or 850nm LED irradiation showed a significant ROS scavenging effect and significantly reduced TUNEL-positive cells by 45.7% and 37.8%, respectively, compared to cells treated only with H2O2. In the result of flow cytometry, the number of cells in the late apoptosis stage was about 2.3- and 1.8-fold lower than that of the cells treated with H2O2 only, but there was no significance. The Bax/Bcl-2 ratio of cells irradiated with 630 nm or 850 nm LED was significantly lower than that of cells treated with H2O2 only, and the expression of procaspase-3 and cleaved PARP was also significantly expressed in the direction of suppressing cell death. In conclusion, the ROS scavenging activity by 630 nm or 850 nm LED irradiation, leading the expression of cell death pathway proteins in the direction of inhibiting cell death.

In this study, a case of acute cattle death was investigated. The pathogen was identified, and its molecular characteristics and vector were analysed. This study provides a reference for the prevention and control of babesiosis and the healthy breeding of cattle. In this study, unengorged and engorged Rhipicephalus microplus ticks were collected from the Chongqing area. The unengorged ticks were cultured on cattle under laboratory conditions, and the engorged ticks were cultured to lay eggs. In the process, the cattle suddenly died at 12 days from the bite of an unengorged R. microplus tick. In addition, the larvae hatched from R. microplus eggs, which were cultured on the other cattle, and the experimental cattle died in approximately 14 days. Blood was collected from a second dying and stored at 4 ℃ for one week. Two millilitres of anticoagulated blood was injected subcutaneously into the third cow without piriformis infection. On the fourth day, the body temperature rose to 41 ℃ with slight lymphadenopathy. On the fifth day, the cow suddenly fell and died approximately 4 hours later. DNA was extracted from the blood of all dead cattle and amplified by PCR with piriformis universal primers. The results showed that the cattle were infected with Babesia bovis. The phylogenetic tree based on 18S rRNA showed that the Chongqing strain of B. bovis, which caused the death of cattle, was closely related to the Yunnan strain in China and had the same taxonomic status as the Spanish strain. This case report will draw people's attention to B. bovis once again, and positive control measures should be taken to reduce the losses of farmers to achieve the goal of healthy breeding.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analyzed, among the arboviruses studied, the hepatic involvement in cases of YF showed greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis and apoptosis were classified as degree of tissue damage from severe to very severe. The pathological abnormalities associated with infection by YFV, DENV, and CHIKV showed predominance of changes in the midzonal area. We also noted that in among of the arboviruses studied, liver involvement in cases of YFV infection was more intense.

The ATP synthase is a mitochondrial complex embedded in the inner mitochondrial membrane. The enzyme is under the double genetic control of the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Fatal human diseases have been associated with defects in ATP synthase (Complex V) activity linked to mtDNA or nDNA pathogenetic variants in genes encoding structural subunits or assembly factors. Mitochondrial post-translational modifications of key amino acids, reduced/increased subunit expression, or protein to protein ATP synthase interaction, are also some of the mechanisms involved in the age-related disease pathway. All the major neurodegenerative diseases: Parkinson’s, Alzheimer’s and motor neuron diseases such as Amyotrophic Lateral Sclerosis highlight an impaired ATP generation in a mechanism involving the permeability transition pore that triggers a cellular homeostasis failure responsible for different forms of regulated cell death. In this review, we will explore ATP synthase assembly and function in physiological and pathological conditions by referring to the recent cryo-EM studies and by exploring human diseases models.

The original purpose of this article was to modify the original SIR equations to allow for a direct source of infection (without which the original equations would have no solutions unless one starts with an already infected population) and also to see to what extent one could obtain multiple outbreaks of an infectious disease. In the course of developing the basic ideas several other factors arose to take prominent roles.Perhaps one of the more salient factors is the point that choosing an arbitrary time to change conditions from say a lock-down for the population to a less stringent social behavior, such as allowing partial or complete opening of businesses and schools, etc. should be based on knowledge of the disease and its evolution. Such decisions are usually made by politicians who have less than full information concerning the consequences of their actions. Several examples are given to illustrate these points.

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

Societal changes have had effects on deaths from all causes in Russia. Up until now, deaths from all causes have been well researched, although several inconsistencies persist on the contributions of researchers. This study assessed research output, trends and topics that shaped deaths from all causes studies in Russia. Using bibliometric and topic modelling approaches, deaths from all causes in Russia published from 1914 to date was analysed using data on publications, citations, journals, keywords co-occurrence, year of publication, institutional affiliations, and country of origin from Scopus. Overall results indicate a steady growth of publications in Russia was documented after 1985. The h-index of some top 10 authors did not surpass single digits. A network visualisation map showed that ‘Russia’, ‘male’, ‘mortality’ and ‘human’ were the most commonly encountered vital terms. Of the ten most prolific authors, McKee M, Shkolnikov VM, Bobak M, Samorodskaya IV and Andreev E were the first five. Although the top 10 journals researching on death causes in Russia were Russian, these journals were not included in the most cited journals. The most prolific institutions studying deaths in Russia included; Tehran University of Medical Sciences, London School of Hygiene and Tropical Medicine, University College London, Max Planck Institute for Demographic Research and National Research University-Higher School of Economics. Findings suggest that deaths from all causes research attention in Russia increased in recent years, but the number of publications and research related engagements (e.g., networking and/ collaboration) does not match-up to other countries (e.g., UK, US, Germany). This research lag calls for more collaborative research between public health disciplines and networking among researchers (i.e., both national and international).

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. Conclusion: In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at

(1) Background: Urinary tract infections (UTIs) are an important cause of perinatal and maternal morbidity and mortality. The aim of this study was to describe and compare the main pregnancy outcomes among pregnant patients with complicated and uncomplicated UTIs; (2) Methods: This retrospective study included 183 pregnant patients who were evaluated for uncomplicated UTIs and urosepsis in the Urology Department of ‘C.I. Parhon’ University Hospital, and who were followed up at a tertiary maternity hospital- ‘Cuza-voda’ from Romania between January 2014 and October 2023. The control group (183 patients) was randomly selected from the patient’s cohort who gave birth in the same time frame at the maternity hospital without urinary pathology. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Our results indicated that patients with urosepsis had increased risk of premature rupture of membranes (aOR: 5.59, 95%CI: 2.02- 15.40, p&lt; 0.001) and preterm birth (aOR: 2.47, 95%CI: 1.15- 5.33, p= 0.02). We could not demonstrate a statistically significant association between intrauterine growth restriction and preeclampsia with the studied urological pathologies. (4) Conclusions: Careful UTIs screening during pregnancy is needed for preventing maternal-fetal complications.

We aimed to investigate the clinical results following poor-quality embryo transfer and the parameters to foresee the prognosis. In this study, 2123 cycles that had day 3 and day 5 single-fresh embryo with a poor-quality embryo transfers and a good-quality embryo transfers were compared. The cycles according to transfer day were evaluated by conducting a subgroup analysis. The correlation between all the obtained demographic characteristics, controlled ovarian stimulation parameters and cycle results were analysed. Clinical pregnancy was established in 53 patients that underwent transfer in the poor-quality embryo group (14.9%). Of these patients, 36 had live birth (live birth rate per clinical pregnancy 67.9%). In cleavage-stage embryos, live birth rates per clinical pregnancy were higher in poor-quality blastocyst transfer. When analysing the factors affecting live births in poor-quality embryo group, as the total gonadotropin dose increases, the probability of live birth decreases, as in the probability of hCG positivity. In conclusion; although the probability of pregnant is low, when clinical pregnancy is established, there is a high chance of having a live birth after poor-quality embryo transfers. This could be regarded as an acceptable option in cycles when only poor-quality embryos were available.

Worldwide, the cesarean section rate has steadily increased from 6.7% in 1990 to 21.1% in 2018 and is expected to rise even more. World Health Organization propose the adoption of the Robson classification system as a global standard for monitoring, evaluating, and comparing delivery rates. The purpose of the current study is to use the Robson classification system to investigate how, independently of medical factors, the day of the week and time of delivery may affect the mode of birth. In the sample analysis, we included the records of 8572 women giving birth in one private health facility in Greece. Over 60% of deliveries during the study period were performed by a cesarean section and 8.5% of deliveries were performed by operative vaginal delivery. The results of this study indicate that the lowest birth rates are observed on Monday, Saturday, and Sunday. In Robson category 1 women are 73% more likely to deliver by cesarean section between 08:00 a.m. - 03:59 p.m. compared to those who give birth between 12:00 a.m. - 07:59 a.m. Also, women in group 5.1 are 16.7 times more likely to deliver by cesarean section in the morning compared to overnight deliveries. These result point out two non-clinical variables that influences the CS rate. The Robson classification system was a useful tool for the above comparisons.

Background: The presence of a skilled health professional at delivery is critical to reduce infant and maternal mortality. Health development plans and strategies, especially in developing countries, consider equity in access to maternal health care services as a priority. This study aimed to measure and analyze the inequality in the use of skilled births attendance services in Mauritania. The study identifies the inequality determinants and to explore its changes over the period 2007–2015. Methods: The concentration curve, concentration index, decomposition of the concentration index and Oaxaca-type decomposition technique were performed to measure socio-economics related inequalities in skilled birth attendance services utilization and identify contribution of different determinants to such inequality as well as the changes in inequality overtime using data from Mauritania Multiple Indicator Cluster Surveys (MICS) 2007, 2011 and 2015. Results: The concentration index for skilled birth attendance services utilization dropped from 0.6324 [P < 0.001] in 2007 to 0.5852 [P < 0.001] in 2015. Prenatal care, household wealth Status and urban-rural location made the biggest contributions to socio-economic related inequalities. Decomposition of the concentration index and Oaxaca-type decomposition revealed changes prenatal care, rural-urban location made positive contributions to decline in inequality. However, alternation in household wealth score, woman’s age, her education level and the number of living children pushed the equality toward deterioration. Conclusion: Clearly, the pro-rich inequality in skilled birth attendance is high in Mauritania despite a slight decrease during the study period. Policy actions on eliminating urban-rural and wealth index disparity should target increase access to skilled birth attendance. Multisectoral Policy actions is needed to improve social determinants of health and to remove health system bottlenecks including socio-economic empowerment of women and girls, enhancing availability and affordability of Reproductive and Maternal Health commodities, improving availability of obstetrical providers in rural area, promoting a better distribution and quality of health infrastructure particularly health posts and health centers, and replacing user fees by an equitable, efficient and sustainable financing scheme under an universal health coverage vision.

There is accumulating evidence that prenatal exposure to air pollution disturbs fetal growth and development, but little is known about these effects in cold climates or their season-specific or joint effects. Our objective was to assess independent and joint effects of prenatal exposure to specific air pollutants on the risk of low birth weight (LBW). We utilized the 2568 children of the Espoo Cohort Study, born between 1984 and 1990, and living in the City of Espoo. We conducted stratified analyses for births during warm and cold seasons separately. We analyzed the effect estimates using multi-pollutant Poisson regression models with risk ratio (RR) as the measure of effect. The risk of LBW was related to exposure to CO and (adjusted RR 1.44, 95% CI: 1.04-2.00) and exposure to O3 in the spring-summer season (1.82, 1.11-2.96). There was also evidence of synergistic effects between CO and O3 (relative risk due to interaction, RERI, all year 1.08, 95% CI: 0.27-4.94, spring-summer 3.97, 2.17-25.85) and PM2.5 and O3 (all year 0.72, -0.07-3.60, spring-summer 2.80, 1.36-19.88). We present new evidence of both independent and joint effects of prenatal exposure in a cold climate on the risk of LBW at low levels of air pollution.

The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activated death receptors on targets cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including the ones for receptor mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45h and next we treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly synergized in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells this pro-apoptotic effect was completely lost. Therefore, the combination of ActD+Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112 and actinomycin D + idasanutlin had similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD+Nut3a+FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Vibrio parahaemolyticus is an important human pathogen that is currently the leading cause of shellfish-borne gastroenteritis in the world. Particularly, the pandemic strain has the capacity to induce cytotoxicity and enterotoxicity through its Type 3 Secretion System (T3SS2) that leads to massive cell death. However, the specific mechanism by which T3SS2 induces cell death remain unclear and the contribution in mitochondrial stress is not fully understood. In this work, we evaluated the contribution of T3SS2 of V. parahaemolyticus to generate mitochondrial stress and cell death during infection in human intestinal HT-29 cells. To evaluate this, infection assays were carried out to evaluate mitochondrial transition pore opening, mitochondrial fragmentation, ATP quantification, and cell viability during infection. Our results showed that the Δvscn1 (T3SS2+) mutant strain contributes to generating the sustained opening of the mitochondrial transition pore. Furthermore, it generates perturbations in the ATP production in infected cells, leading to a significant decrease in cell viability and loss of membrane integrity. Our results suggest that T3SS2 from V. parahaemolyticus plays a role in generating mitochondrial stress and cell death in human intestinal HT-29 cells. It is important to highlight that this study represents the first report indicating the involvement of T3SS2 from V. parahaemolyticus in generating mitochondrial stress, its impact on the mitochondrial pore, and its effect on ATP production in human cells.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

Ferroptosis is a recent form of non-apoptotic cell death, which occurs due to imbalance of iron homeostasis (iron overload). Oxidative stress due to the impairment of the antioxidant system is a major pathophysiology during ferroptosis, which eventually results in lipid peroxidation. The cellular and physiological biomarker of ferroptotic cell death includes major alteration in the glutathione peroxidase 4 (GPX4) antioxidant system and lipid peroxidation induced loss of plasma membrane integrity. This review elaborates the mechanism of oxidative stress which triggers ferroptosis.

Background: The Covid-19 pandemic has globally impacted the lives of individuals, families, and children. In Italy, measures such as lockdowns and distance learning were implemented in schools, which affected the mental health of children and families. Methods: This article employs qualitative methodology to explore the experiences of children, parents, and teachers during the pandemic and lockdown, as well as the implementation of a death education project aimed at primary school children to help them process emotions and losses experienced during this period. Results: Distance learning posed challenges to the learning process and exacerbated social inequalities. Children suffered from limited social contact with friends and experienced negative emotions, including anger, fear, and concern for the health of their loved ones. The death education project provided a safe space for emotional expression and facilitated the acquisition of coping strategies. Open communication between adults and children about illness and death proved effective in mitigating the psychological impacts of loss and preventing traumatic bereavement. Conclusions: The findings highlight the utility of death education in enhancing children's ability to express their emotions and approach the topic of death morefrankly.

Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye, and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the proinflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. : ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective affect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.

Background. The main impetus behind the worldwide Covid-19 vaccination campaign in 2021 was to reduce the mortality attributed to SARS-CoV-2 infection in the preceding year. Nevertheless, rigorous analyses of the mortality benefits conferred by this massive vaccination effort have been lacking. Methods Statistics offers us an essential methodological approach for measuring the impacts of Covid-19 vaccination on public health. The mathematical relation between vaccinated-alive groups can be repeated between vaccinated-dead groups with relatively high statistical reliability because of the large population numbers involved. This method also confers greater statistical usefulness because it eliminates the Simpson effect. Results Calculations were performed for each of the following five(5) four-week intervals: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2021), weeks 47-50 (2021), and weeks 50(2021)-1(2022). The results obtained confirm that the mortality of the vaccinated coronavirus-infected groups was 14.5% higher on average than the mortality of non-vaccinated coronavirus-infected groups. Conclusions Vaccinated infected groups appear to have higher average mortality than their non-vaccinated infected counterparts. The findings suggest the legitimacy of extending the statistics between vaccinated living and vaccinated dead individuals for different age groups. Calculating the impact of Covid-19 vaccination on the mortality rate is a necessary step towards satisfying the first principle of medicine: “Primum non nocere”, “Do no harm”.

Previous research suggests that the senescence and death of the replaceable bud in chestnut cultivar (cv.) ‘Tima Zhenzhu’ involves programmed cell death (PCD). However, the molecular network responsible for regulating replaceable bud PCD is poorly characterized. Here, we performed transcriptomic profiling of the chestnut cv. ‘Tima Zhenzhu’ replaceable bud before (S20), during (S25), and after PCD (S30) to ascertain the molecular mechanism underlying the PCD process. A total of 5,779, 9,867, and 2,674 differentially expressed genes (DEGs) were discovered upon comparison of S20 vs. S25, S20 vs. S30, and S25 vs. S30, respectively. Approximately 6,137 DEGs common to at least two comparisons were selected for GO and KEGG enrichment analyses to interrogate the main corresponding biological functions and pathways. GO analysis showed that these common DEGs could be divided into three functional categories, including 15 cellular components, 14 molecular functions, and 19 biological processes. KEGG analysis found that “plant hormone signal transduction” included 93 DEGs. Overall, 441 DEGs were identified as related to the process of PCD. Most of these were found to be genes associated with ethylene signaling, as well as initiation and execution of various PCD processes. A hypothetical model, consisting of three overlapping processes, is proposed for the replaceable bud PCD: First, ethylene signaling is activated during preparation for PCD, in order to regulate the activity of downstream targets. Next, during PCD initiation, the up-regulation of several TFs (including MYB, MADS-box, bHLH, and NAC TFs) induces an increase in cytochrome c expression and in the cytosolic Ca2+ content, activating the Ca2+-dependent signaling cascade. Finally, during PCD execution, the process of autophagy and the activity of proteases (i.e., cysteine proteinases RD21A-like, metacaspase-9-like, vacuolar-processing enzyme-like, and senescence-associated proteins for hydrolysis) work synergistically to clear the cell of cellular components. When this process is complete, the replaceable bud senesces and dies.

Excessive activation of frog eggs (overactivation) is a pathological process that renders eggs unfertilizable. Its physiological inducers are unknown. Previously, oxidative stress was shown to cause time- and dose-dependent overactivation of Xenopus laevis frog eggs [1]. Here, we demonstrate that the oxidative stress-induced egg overactivation is a calcium-dependent phe-nomenon which can be attenuated in the presence of the selective calcium chelator BAPTA. Degradation of cyclin B2, which is known to be initiated by calcium transient in fertilized or parthenogenetically activated eggs, can also be observed in the overactivated eggs. Decline in mitochondrial membrane potential, ATP depletion and termination of protein synthesis manifest in the eggs within one hour of triggering overactivation. These intracellular events occur in the absence of caspase activation. Furthermore, plasma membrane integrity is compromised in the overactivated eggs, as evidenced by ATP leakage and egg swelling. In sum, our data demonstrate that oxidative stress-induced overactivation of frog eggs causes fast and dramatic disruption of cellular homeostasis, resulting in robust and expedited cell death by a calcium-dependent non-apoptotic mechanism.

Fire-related deaths are issues for forensic pathologists particularly in ascertaining if death occurred before or during fire. The authors highlight a unique bronchiolar epithelial cytological clue (nuclear heat-induced elongation) determined by active inhalation of hot gases and fumes, not yet described in the literature at distal small airways level.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

The study explored the community perception of maternal deaths influenced by natural disaster, practice of maternal complications during natural disaster among the rural population in Bangladesh. It also explored the challenges faced by the community for providing health care and referring the complicated pregnant mothers during disaster. Three focus group discussions (FGDs) and eight in-depth interviews (IDIs) were conducted in the marginalized rural communities in the flood-prone Khaliajhuri sub-district, Netrakona district, Bangladesh. Flood is one of the major risk factors for influencing maternal death. Pregnant mothers seriously suffer from maternal complication, lack of antenatal checkup and even any doctor during flood. During the time of delivery, it is difficult to find even a skilled attendant and referring the patient with delivery complications to the healthcare facility. Boat is the only mode of transport. Majority maternal deaths occur on the boats during transfer from the community to the hospital. The rural people feel that the maternal deaths influenced by natural disaster are the natural phenomena. It needs some pre-preparation to support pregnant women during the disaster. There is unawareness of maternal health, related care and complications during disaster among the local health service providers and volunteers.

Hyperkalemia burden in non-dialysis CKD under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalemia (sK≥5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of ESKD and death after visit 2. Age was 65±15 y, eGFR 35±17 mL/min/1.73 m2, proteinuria 0.40 (0.14-1.21) g/24h. In the two visits sK was 4.8±0.6 and levels ≥6 mEq/L were observed in  4%. Hyperkalemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis [sub-hazard ratio-sHR, 95%Confidence Interval-CI] evidenced that new onset [sHR 1.34, 95%CI 1.05-1.72] and persistent [sHR 1.27, 95%CI 1.02-1.58] hyperkalemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

(1) Background: To estimate resistance, reactance and phase angle values among moderate preterm infants and their variation according to neonatal and maternal characteristics and nutritional intake. (2) Methods: This was a cohort that evaluated 43 moderate preterm infants using bioelectrical impedance analysis. The study variables included resistance, reactance and PA measurements, in addition to classification of nutritional intake. (3) Results: The mean resistance was 602.0+118.2 Ω, reactance was 57.2 Ω (IIQ = 42.6-65.2) and phase angle was 522° (IIQ = 4.1-6.6). Lower resistance values were found in the presence of risky pregnancy (532.2+111.9 Ω vs 650.9+97.9 Ω, p&lt;0.001) and lower reactance values, in the presence of harmful maternal lifestyle habits at both the first (p=0.01) and second assessments (p=0.01). Eight preterm infants were considered to have insufficient nutritional intake (23.5%); 17, sufficient (50.0%) and 9, partially sufficient (26.5%). There was less reactance among preterm infants with insufficient nutritional intake (p &lt; 0.001). (4) Conclusions: The bioelectrical impedance analysis measurements were within the range of values reported in other studies. There was an association between full diet and adequate nutritional intake with higher resistance values, and a lower reactance value was associated with the presence of risky pregnancy and harmful maternal lifestyle.

This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

The persistent burden of chronic hepatitis B among ≤5-year-old children in Africa suggests missed opportunities for controlling mother-to-child transmission (MTCT) of the hepatitis B virus (HBV). This scoping review maps the evidence base on the risk of HBV MTCT, the status of HBV MTCT mitigation strategies including hepatitis B birth-dose vaccination, and the role of systems complexity on the suboptimal adoption and performance of hepatitis B birth-dose vaccination programs in Africa. Overall, 88 peer-reviewed and grey literature sources published between 2000–2022 were included in this review. The evidence base consistently argues for a growing risk of HBV MTCT amidst the HIV co-epidemic in the region. Without universal HBV screening programs integrated within broader antenatal care services, current selective hepatitis B birth-dose vaccination is unlikely to effectively interrupt HBV MTCT. We underscore critical health systems-related barriers to universal adoption and optimal performance of hepatitis B birth-dose vaccination programs in the region. To better conceptualize the role of complexity and system-wide effects on the observed performance of the program, we propose an adapted systems-based logic model. Ultimately, exploring contextualized complex systems approaches to scaling-up universal hepatitis B birth-dose vaccination programs should form an integral part of the regional research agenda.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential in sustaining premature infants until they transition to enteral feeds. There is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born &lt;29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN as compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs enteral feeds at p&lt;0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants with longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with initiation of enteral feeds. Infants on enteral feeds had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting a nutritional benefit of an enteral feeding regimen.

Introduction: In the marginalised countries most neglected health issue is Newborn mortality. A study was undertaken to assess the influence of factors and newborn care practices influencing newborn health in the rural area of Bareilly district. Methodology: The Descriptive cross-sectional study was organized in the rural areas of Bareilly. Study participants were selected based on the mothers who gave birth to a baby during the last six months. The mothers who delivered in that area within six months were included, and using the semi-structured questionnaire, data was collected. Data analyzed using Microsoft Excel and SPSS 2021 version for windows. Results: Mothers initiating early breastfeeding were more commonly 78 (52.3%) observed in the younger mothers at 24-29 years, followed by 48(32.3%) at 30-35 years, the difference was statistically significant (p<0.05). Delayed bathing was observed in nearly 125 (70.1%) three fourth in the age of 24-29 years, followed by 29 (16.8%) in the age period 30-35 years. It was observed that unsafe cord care practices were observed more among 8(53.4%) nuclear families than 7(46.6%) joint families, and it was found to be statistically insignificant. Conclusion: The practice of essential newborn care still needs to improve in Bareilly; there is a need to create awareness to the mothers and family members on newborn and early neonatal care aspects, such as promoting exclusive and early initiation of breastfeeding and delayed bathing practices.

In Japan, the prevalence of low birth weight (LBW) has been estimated to be approximately 10%, which is the highest among developed countries. This high prevalence might affect the prevalence of LBW-associated diseases in the adult population of Japan. Recently, LBW has been recognized as a contributing factor to post-adaptive focal segmental glomerulosclerosis (FSGS) in adulthood; however, few reports to date have evaluated the clinical and pathological characteristics of post-adaptive FSGS. A 13-year-old girl was referred to our hospital owing to mild proteinuria, which was detected at a school urinary screening. She was born at a gestational age of 23 weeks, with a very LBW of 630 g. Dipstick urinalysis revealed grade (2+) proteinuria. Her serum creatinine level was 1.02 mg/dL, and she was diagnosed as having stage 2 chronic kidney disease (CKD). Her serum uric acid level was 7 mg/dL. Her mother and 16-years old brother had hyperuricemia, too. A percutaneous renal biopsy leads to a diagnosis of FSGS. After 3 years of treatment with an angiotensin receptor blocker, her proteinuria decreased. However, her serum creatinine level was 1.07 mg/dL, and she still had stage 2 CKD. We considered that in this patient, the first hit was her LBW, and the second hit was hyperuricemia. The second hit might be associated with the development of CKD. The birth history of patients is not usually confirmed by nephrologists. Our case demonstrates that obtaining information regarding the preterm birth and LBW of patients is important in the diagnosis of noncommunicable diseases, because school urinary screening is not routinely performed in countries other than Japan.

Background The link between age at marriage and first birth in explaining completed family size is not always direct, due to heterogeneity in circumstances, that compel individual women to marry or initiate childbearing at a particular age. We analyzed data for 1020 women aged 45-49 in 2014 of the 1965-1969 birth cohort from the 2013-14 Zambia Demographic and Health Survey (ZDHS). Methods We fitted a bivariate and multivariate multinomial logistic regression to establish the relationship between a mother’s age at first marriage and at first birth on completed family size (CFS). Chi-square test of proportions measuring differences in proportions and relative risk ratios (RRR) with confidence intervals at 95% are reported. Results Our results show that the average CFS was 6.7 (95% CI: 6.5 – 6.9) among women completing their reproductive span in 2014 with mean age at first marriage and birth being 18.3 years (95% CI: 18.0 – 18.5) and 18.9 years (95% CI: 18.7 – 19.1) respectively. Women marrying at younger ages and having their first birth at younger ages were more likely (RRR: 1.187; 95% CI: 1.138-1.239 and RRR: 0.195; 95% CI: 0.074-0.511 respectively) to have higher CFS than their compatriots that initiated both marriage and childbearing at or after age 22 controlling for covariates as presented in the controlled model. The independent effects model shows that the risk of having 1-3 children compared to 6 or more children was lower (RRR: 0.073; 95% CI: 0.009-0.611; RRR: 0.136; 95% CI: 0,046-0.402 and RRR: 0.421; 05% CI: 0.135-1.312) for women whose ages at first marriage were <15, 15-18 and 19-21 respectively relative to 22+. Women with 1-3 children were 2.5 times more likely to use contraception than women with 6 or more children. Conclusion Having no education, being a rural resident and having a medium household wealth all increase the risk of having higher CFS. Women that marry before age 19 have a higher likelihood of having 6 or more children by the end of their reproductive period. The study concludes that apart from a woman’s age at first marriage and first birth, a complex network of factors interact to determined CFS.

Different cohort studies documented a lower glomerular filtration rate (GFR) in former extremely low birth weight (ELBW, <1000 g) neonates throughout childhood when compared to term controls. The current aim is to pool these studies to describe the GFR pattern over the pediatric age range. To do so, we conducted a systematic review on studies reporting on GFR measurements in former ELBW cases while GFR data of healthy age-matched controls included in these studies were co-collected. Based on 248 hits, 6 case-control and 3 cohort studies were identified, with 444 GFR measurements in 380 former ELBW cases (median age 5.3-20.7 years). The majority were small (17-78 cases) single center studies, with heterogeneity in GFR measurement (inulin, Cystatin C or creatinine estimated GFR formulae) tools. Despite this, the median GFR (ml/kg/1.73m²) within case-control studies was consistently lower (-13, range -8 to -25%) in cases, so that a relevant minority (15-30%) has a eGFR<90 mgl/kg/1.73m²). Consequently, this pooled analysis describes a consistent pattern of reduced eGFR in former ELBW cases throughout childhood. Research should focus on perinatal risk factors for impaired GFR and long-term outcome, but is hampered by single center cohorts, study size, and heterogeneity of GFR assessment tools.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since its emergence and is causing the disease COVID-19. According to WHO, this is a zoonotic disease. Several cases have already been discovered where companion animals were affected due to virus spillover from humans, however, the symptoms are mild in most cases. We report the first documented case of SARS-CoV-2 infection and death of a domestic cat (Felis silvestris catus) in Hungary, where no other disease could be detected.

Fusarium oxysporum f. sp. lycopersici (Fol) causes vascular wilt disease in tomato. Upon colonization of the host, Fol secretes many small effector proteins into the xylem sap to facilitate infection. Besides known SIX (Secreted In Xylem) proteins, the identity of additional effectors that contribute to Fol pathogenicity remains largely unexplored. We have performed a deep RNA-sequencing analysis of Fol race 2-infected tomato, used the sequence data to annotate a published genome assembly generated via PacBio SMRT sequencing of the Fol race 2 reference strain Fol4287, and analysed the resulting transcriptome to identify Fol effector candidates among the newly annotated genes. We examined the Fol-infection expression profiles of all 13 SIX genes present in Fol race 2 and identified 27 new candidate effector genes that were likewise significantly upregulated upon Fol infection. Using Agrobacterium-mediated transformation, we tested the ability of 22 of the new candidate effector genes to suppress or induce cell death in leaves of Nicotiana benthamiana. One effector candidate designated Fol-EC19, encoding a secreted guanyl-specific ribonuclease, was found to trigger cell death and two effector candidates designated Fol-EC14 and Fol-EC20, encoding a glucanase and a secreted trypsin, respectively, were identified that can suppress Bax-mediated cell death. Remarkably, Fol-EC14 and Fol-EC20 were also found to suppress I-2/Avr2- and I/Avr1-mediated cell death. Using the yeast secretion-trap screening system, we showed that these three biologically-active effector candidates each contain a functional signal peptide for protein secretion. Our findings provide a basis for further understanding the virulence functions of Fol effectors.

This paper presents the results of quantitative research regarding the predictive model of citizens' attitudes about the risks of introducing the death penalty in the Republic of Serbia legal system. The research was conducted with the use of a questionnaire that was requested and then collected online from 427 people in June 2021. A multivariate regression analysis was used, identifying the extent to total scores of the main dependent variables (introducing the death penalty; trust in the legal system; advantages of introduction; disadvantages of introduction scores) were associated with five demographic and socio-economic variables: gender, marital, education, income, and age. We tested the central hypothesis of which gender is predicting variables citizens' attitudes about the risks of introducing the death penalty in the legal system of Serbia. The findings revealed that gender and educational level were the most effective predictors of the research variables under question. The majority of respondents support the introduction of the death penalty and the most important predictor of disadvantages of introducing the death penalty in the legal system is age. Based on the findings that there are major differences in the citizens' attitudes about the risks of introducing the death penalty in the legal system, policies, strategies, and regulations must take into account these very important findings.

Abstract: As innovative way to express grief, social media posts about the deceased have become fairly common. However, few studies examined grief photos commonly posted. The purpose of the present study was to examine such pictures, as well as the motivation and reactions of those who posted, among Italians and Americans. Surveys were sent to both Italian and U.S. participants. The U.S. group yielded 262 responses (Mean age = 22 years; 81% female), the Italian yielded 51 (Mean age = 32. Several key issues emerged, such as the need to receive empathic support from other users, the desire to maintain continuing bonds, the wish to remember the deceased, and the desire to share beauty and symbolic pictures. The images were analyzed using content analysis. Both samples posted photos to remember and to enhance their posts. A strong preference for pictures with a positive emotional connotation appeared, depicting the deceased in a conjoint appearance with the participant. Results suggest that imagery used for the expression of grief in social media sites, an “iconography of grief,” is a popular means of expression for grievers.

Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: we performed CMR in 49 HCM patients, 30 non-HCM hypertrophy and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to the 25% of diastole. Left ventricular mass, mean and standard deviation (SD) of WT, maximal WT, minimal WT and their difference, were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating 8 hearts with HCM, 10 with coronary artery disease and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95%CI 0.89-0.98). This was particularly evident in female population of HCM (AUC=0.998), with 100% specificity (95%CI 85-100%) and 96% sensitivity (95%CI 79-99%). Using this parameter, at PMCMR all the 8 patients with HCM were correctly identified with no false positive. Conclusions: PMCMR allows to identify HCM as cause of sudden death using the SD of WT >2.4 as diagnostic parameter.

Standard evolutionary theory, supported by mathematical modelling of outbred, dispersed populations predicts that ageing is not an adaptation. We recently argued that in clonal, viscous populations, programmed organismal death could promote fitness through social benefits and has, in some organisms (e.g. Caenorhabditis elegans), evolved to shorten lifespan. Here we review previous adaptive death theory, including consumer sacrifice, biomass sacrifice, and defensive sacrifice types of altruistic adaptive death. In addition we discuss possible adaptive death in semelparous fish, coevolution of reproductive and adaptive death, and adaptive reproductive senescence in C. elegans. We also describe findings from recent tests for the existence of adaptive death in C. elegans using computer modelling. Such models have provided new insights into how trade-offs between fitness at the individual and colony levels mean that senescent changes can be selected traits. Exploring further the relationship between adaptive death and social interactions, we consider examples where adaptive death results more from action of kin than from self-destructive mechanisms and, to describe this, introduce the term adaptive killing of kin.

The cytostatic agent hydroxyurea (HU) has proven to be beneficial for a variety of conditions in the disciplines of oncology, hematology, infectious disease and dermatology. It disrupts the S-phase of the cell cycle by inhibiting the ribonucleotide reductase enzyme, thus blocking the transformation of ribonucleotides into deoxyribonucleotides, a rate limiting step in DNA synthesis. HU is listed as an essential medicine by the World Health Organization. Several studies have indicated that HU is well tolerated and safe in pregnant women and very young pediatric patients. To our knowledge, only a few controlled studies about the adverse effects of HU therapy have been done in humans. Despite this, the prevalence of central nervous system abnormalities, including ischemic lesions and stenosis have been reported. This review will summarize and present the effects of HU-exposure on the prenatal and perinatal development of the rat cerebellar cortex and deep cerebellar nuclei neurons. Our results call for the necessity to better understand HU effects and define the administration of this drug to gestating women and young pediatric patients.

Background: In 1962, Susser and Stein observed that the mortality rates of peptic ulcers in England and Wales increased markedly in the 1910s, maintained at a high level during the 1910s-1940s, and began to decline steadily since the early 1950s. They termed this epidemic pattern a birth-cohort phenomenon, but its mechanism has never been elucidated. Susser and Stein speculated that the occurrences of extraordinary social environmental factors roughly fit the fluctuations, but the role of environmental factors in peptic ulcers has never been identified. Objectives: This study aims to elucidate the mechanism of the birth-cohort phenomenon of peptic ulcers and identify the role of environmental factors in the disease. Methods: Starting from an etiology identified recently, this study uses the two inverse operations in calculus, differentiation, and integration, to analyze the existing data. First, a fluctuation curve in the birth-cohort phenomenon is differentiated into multiple annual mortality rates caused by individual environmental factors. Second, these annual mortality rates are integrated to reproduce the fluctuation curve in the birth-cohort phenomenon. Results: The differentiation reveals a parallel relationship between the psychological impacts of environmental factors and the mortality rates of peptic ulcers, whereas the integration reproduces a representative fluctuation curve in the birth-cohort phenomenon. The successive occurrences of multiple social environmental factors from the 1910s to 1940s maintained the increase in mortality rates, while the sustained improvements in living environments explained the steady decline of the mortality rates from the early 1950s. Conclusion: The parallel relationship suggests a causal role of environmental factors in peptic ulcers, whereas the reproduction of a representative fluctuation curve indicates that multiple environmental factors caused the birth-cohort phenomenon by Superposition Mechanism. Significantly, this study challenges the current reductionist approach used to study disease in modern medicine by demonstrating the effectiveness of an opposite methodological concept focused on integration.

Background: Little is known about the natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants, further hampered by the lack of noninvasive investigations. We aimed at developing a non-invasive tool for the study of IgE and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases (cow’s milk allergy, asthma, or atopic dermatitis) during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. sIgE responses were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex containing whole and molecular allergens and confirmed by capillary Western blot with nano-immunoassay. The local eosinophilic component was investigated by measuring the concentration of EDN. Results: The multiplexed allergen assay detected sIgE in all samples. Confirmation was obtained with Western blot. Frequency and levels of sIgE in neonatal fecal samples differed between infants who developed IgE-mediated diseases and controls. Neonatal fecal sIgE directed to milk proteins predicted later development of cow’s milk allergy (specificity 88%, sensitivity 78%). Allergen specificity of neonatal fecal sIgE was associated with later development of cow’s milk allergy and asthma. Neonatal fecal EDN levels predicted the development of IgE-mediated diseases (sensitivity 100%, specificity 75%). Conclusion: Non-invasive investigation of neonatal fecal sIgE is a promising tool for the prediction of subsequent development of IgE-mediated diseases.

Abstract: Objective: To assess both individual and interactive effects of prenatal medical conditions depression and Diabetes, and health behaviors including smoking during pregnancy on infant birth defects. Methods: The data for this research study were collected by the Pregnancy Risk Assessment Monitoring System (PRAMS) in 2018. Birth certificate records were used in each participating jurisdiction to select a sample representative of all women who delivered a live-born infant. Complex sampling weights were used to analyze the data with a weighted sample size of 4,536,867. Descriptive statistics were performed to explore frequencies of the independent and dependent variables. Bivariate and multivariable analyses were conducted to examine associations among the independent and dependent variables. Results: The results indicate and significant interaction between the variables smoking and Depression and Depression and Diabetes (OR= 3.17; p-value <0.001 and OR= 3.13; p-value <0.001 respectively). Depression during pregnancy was found to be strongly associated with delivering an infant with a birth defect (OR= 1.31, P-value < 0.001). Conclusion: Depression during pregnancy and its interaction with smoking and Diabetes are vital in determining birth defects in infants. The results indicate that birth defects in the United States can be lowering Depression in pregnant women.