Poxvirus Vaccines: Past, Present, and Future.

Smallpox was a significant cause of mortality for over three thousand years, amounting to 10% of deaths yearly. Edward Jenner discovered smallpox vaccination in 1796, which rapidly became a smallpox infection preventive practice throughout the world and eradicated smallpox infection by 1980. After smallpox eradication, monkeypox vaccines have been used primarily in research and in outbreaks in Africa, where the disease is endemic. In the present, the vaccines are being used for people who work with animals or in high-risk areas, as well as for healthcare workers treating patients with monkeypox. Among all orthopoxviruses (OPXV), monkeypox viral (MPXV) infection occurs mainly in cynomolgus monkeys, natural reservoirs, and occasionally causes severe multi-organ infection in humans, who were the incidental hosts. The first case of the present epidemic of MXPV was identified on May 7, 2022, and rapidly increased the number of cases. In this regard, the WHO declared the outbreak, an international public health emergency on July 23, 2022. The first monkeypox vaccine was developed in the 1960s by the US Army and was based on the vaccinia virus, which is also used in smallpox vaccines. In recent years, newer monkeypox vaccines have been developed based on other viruses such as Modified Vaccinia Ankara (MVA). These newer vaccines are safer and can provide longer-lasting immunity with fewer side effects. For the future, there is ongoing research to improve the current vaccines and to develop new ones. One notable advance has been the development of a recombinant vaccine that uses a genetically modified vaccinia virus to express monkeypox antigens. This vaccine has shown promising results in pre-clinical trials and is currently undergoing further testing in clinical trials. Another recent development has been the use of a DNA vaccine, which delivers genetic material encoding monkeypox antigens directly into cells. This type of vaccine has shown effectiveness in animal studies and is also undergoing clinical testing in humans. Overall, these recent advances in monkeypox vaccine development hold promise for protecting individuals against this potentially serious disease.

Molecular Basis of Müllerian Agenesis Causing Congenital Uterine Factor Infertility-A Systematic Review.

Infertility affects around 1 in 5 couples in the world. Congenital absence of the uterus results in absolute infertility in females. Müllerian agenesis is the nondevelopment of the uterus. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition of uterovaginal agenesis in the presence of normal ovaries and the 46 XX Karyotype. With advancements in reproductive techniques, women with MA having biological offspring is possible. The exact etiology of MA is unknown, although several genes and mechanisms affect the development of Müllerian ducts. Through this systematic review of the available literature, we searched for the genetic basis of MA. The aims included identification of the genes, chromosomal locations, changes responsible for MA, and fertility options, in order to offer proper management and counseling to these women with MA. A total of 85 studies were identified through searches. Most of the studies identified multiple genes at various locations, although the commonest involved chromosomes 1, 17, and 22. There is also conflicting evidence of the involvement of various candidate genes in the studies. The etiology of MA seems to be multifactorial and complex, involving multiple genes and mechanisms including various mutations and mosaicism.

The Molecular Basis of Male Infertility in Obesity: A Literature Review.

The rising incidence of obesity has coincided with rising levels of poor reproductive outcomes. The molecular basis for the association of infertility in obese males is now being explained through various mechanisms. Insulin resistance, hyperglycemia, and changes in serum and gonadal concentrations of adipokines, like leptin, adiponectin, resistin, and ghrelin have been implicated as causes of male infertility in obese males. The effects of obesity and hypogonadism form a vicious cycle whereby dysregulation of the hypothalamic-pituitary-testicular axis-due to the effect of the release of multiple mediators, thus decreasing GnRH release from the hypothalamus-causes decreases in LH and FSH levels. This leads to lower levels of testosterone, which further increases adiposity because of increased lipogenesis. Cytokines such as TNF-α and interleukins, sirtuins, and other inflammatory mediators like reactive oxygen species are known to affect fertility in obese male adults. There is evidence that parental obesity can be transferred through subsequent generations to offspring through epigenetic marks. Thus, negative expressions like obesity and infertility have been linked to epigenetic marks being altered in previous generations. The interesting aspect is that these epigenetic expressions can be reverted by removing the triggering factors. These positive modifications are also transmitted to subsequent generations.

Markers of inflammation in obese pregnant women: Adenosine deaminase and high sensitive C - reactive protein.

Introduction: The worldwide increase in the prevalence of obesity over the years has emerged as a global health concern. The growing rate of obesity in women of child bearing age is particularly a matter of concern. Obesity is considered a risk factor that predisposes an individual to a proinflammatory state through the release of the inflammatory mediators. Recent studies have shown a positive correlation between the severity of inflammation and an increase in adenosine deaminase (ADA) and high sensitivity C- reactive protein (hs-CRP). Obese pregnancy women are at a higher risk for developing inflammation-mediated pregnancy complications like gestational diabetes, preeclampsia, and preterm delivery. Considering the fact that pregnancy, obesity and inflammation are closely linked, this study evaluated the inflammation associated with obesity during pregnancy by estimating changes in ADA and hs-CRP. Materials and methods: The current study aimed to evaluate the levels of inflammation in obese pregnant women compared to non-obese pregnant women by correlating BMI with levels of ADA / hs-CRP. The study also aimed to examine the change in ADA and hs-CRP levels with gestational age (between the 1st and the 3rd trimester) in obese pregnant women as compared to non-obese pregnant women. We also examined whether changes in the levels of ADA correlate with changes in the levels of hs-CRP particularly in obese pregnant women.Blood samples were collected from obese and non-obese pregnant women. ADA activity and hs-CRP levels were estimated by biochemical assays. BMI was evaluated in the 1st trimester and those women with BMI > 30 kg/m2were considered as obese. Thirty subjects were included in each of the two groups. Results: ADA and hs-CRP levels were significantly higher in obese pregnant women in both the 1st and 3rd trimesters compared to non-obese participants (P value<0.05). Statistically significant higher values of ADA and hs-CRP were seen in obese participants in the 3rd trimester compared to the 1st trimester.A significant linear positive correlation was found between BMI and 3rd trimester ADA, and a linear positive correlation between BMI and hs-CRP both in the 1st and 3rd trimester. The relationship between ∆ ADA and ∆ hs-CRP was non- significant. Conclusions: The observations of this study reveal increased inflammatory responses in obese pregnant women and suggests the importance of ADA and hs-CRP as early indicators of obesity-related complications prevailing thereafter, these markers can be useful for clinical diagnosis of impending maternal and neonatal complications.

Van der Knaap Disease (Vanishing White Matter) - Unusual Presentation in a Neonate: A Case Report.

Van der Knaap disease, also known as megalencephalic leukoencephalopathy with subcortical cysts (MLC), is a rare autosomal disorder, with no exact prevalence but more than 150 cases were reported in the literature. It was more prevalent in some ethnicities where consanguinity is common.[1] It is usually characterized by infantile-onset macrocephaly, cerebral leukoencephalopathy and mild neurological symptoms, and a slow course of functional deterioration.[2] Diagnosis is determined by suggestive clinical features and MRI findings that include leukodystrophy and subcortical cysts. Herein, we present a rare occurrence of Van der Knaap disease, in a 24-day-old female neonate with similar MRI findings, who presented with neonatal seizures for evaluation.