Modulation of SLFN11 induces changes in DNA Damage response in breast cancer.

BACKGROUND: Lack of Schlafen family member 11 (SLFN11) expression has been recently identified as a dominant genomic determinant of response to DNA damaging agents in numerous cancer types. Thus, several strategies aimed at increasing SLFN11 are explored to restore chemosensitivity of refractory cancers. In this study, we examined various approaches to elevate SLFN11 expression in breast cancer cellular models and confirmed a corresponding increase in chemosensitivity with using the most successful efficient one. As oncogenic transcriptomic downregulation is often driven by methylation of the promotor region, we explore the demethylation effect of 5-aza-2'-deoxycytidine (decitabine), on the SLFN11 gene. Since SLFN11 has been reported as an interferon inducible gene, and interferon is secreted during an active anti-tumor immune response, we investigated the in vitro effect of IFN-γ on SLFN11 expression in breast cancer cell lines. As a secondary approach to pick up cross talk between immune cells and SLFN11 expression we used indirect co-culture of breast cancer cells with activated PBMCs and evaluated if this can drive SLFN11 upregulation. Finally, as a definitive and specific way to modulate SLFN11 expression we implemented SLFN11 dCas9 (dead CRISPR associated protein 9) systems to specifically increase or decrease SLFN11 expression. RESULTS: After confirming the previously reported correlation between methylation of SLFN11 promoter and its expression across multiple cell lines, we showed in-vitro that decitabine and IFN-γ could increase moderately the expression of SLFN11 in both BT-549 and T47D cell lines. The use of a CRISPR-dCas9 UNISAM and KRAB system could increase or decrease SLFN11 expression significantly (up to fivefold), stably and specifically in BT-549 and T47D cancer cell lines. We then used the modified cell lines to quantify the alteration in chemo sensitivity of those cells to treatment with DNA Damaging Agents (DDAs) such as Cisplatin and Epirubicin or DNA Damage Response (DDRs) drugs like Olaparib. RNAseq was used to elucidate the mechanisms of action affected by the alteration in SLFN11 expression. In cell lines with robust SLFN11 promoter methylation such as MDA-MB-231, no SLFN11 expression could be induced by any approach. CONCLUSION: To our knowledge this is the first report of the stable non-lethal increase of SLFN11 expression in a cancer cell line. Our results show that induction of SLFN11 expression can enhance DDA and DDR sensitivity in breast cancer cells and dCas9 systems may represent a novel approach to increase SLFN11 and achieve higher sensitivity to chemotherapeutic agents, improving outcome or decreasing required drug concentrations. SLFN11-targeting therapies might be explored pre-clinically to develop personalized approaches.

High-risk human papillomaviruses and Epstein-Barr virus in breast cancer in Lebanese women and their association with tumor grade: a molecular and tissue microarray study.

BACKGROUND: High-risk human papillomaviruses (HPVs) are present and can cooperate with Epstein-Barr virus (EBV) to initiate and/or enhance the progression of several types of human carcinomas including cervical as well as head and neck; in parallel, it has been recently pointed out that these oncoviruses can be detected in human breast cancers. Thus, we herein explored the presence/co-presence of high-risk HPVs and EBV in breast cancer in Lebanese women. METHODS: A cohort of 102 breast cancer samples and 14 normal breast tissues were assessed for the presence of HPVs and EBV. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis in addition to tissue microarray (TMA) platform were used in this study. RESULTS: We found the presence of HPV in 66/102 (65%) of our samples, while EBV is present in 41/102 (40%) of the cohort. Additionally, our data showed that high-risk HPV types (52, 35, 58, 45, 16 and 51) are the most frequent in breast cancer in Lebanese women. Meanwhile, we report that high-risk HPVs and EBV are co-present in 30/102 (29%) of the samples; more significantly, our results indicate that their co-presence is associated with tumor grade (p = 0.03). CONCLUSION: Our data revealed that HPVs and EBV are present/co-present in human breast cancer where they may play an important role in its development and/or progression; thus, we believe that further investigations are essential to confirm and elucidate the presence/co-presence of these oncoviruses and the underlying mechanisms of their interaction in breast carcinogenesis.

Child with intellectual disability misdiagnosed as autism: A case study.

Misdiagnosis has become a public health crisis and it is unavoidable in all health care systems. This case study is about a nine year old boy, referred by the special school teacher presenting with the complaints of Autism and slow learning. Contrary to his complaints, the developmental assessment showed that the child had no symptoms of Autism, whereas moderate symptoms of Intellectual Disability were made known. The brief therapeutic plan focused on enhancing his functional level of adaptive behaviour. This case report holds its implication to drift attention of stakeholders working in different health care systems towards the issue of misdiagnosis.

Psychosocial Reactions of Pakistani Students Towards COVID-19: A Prevalence Study.

BACKGROUND: The current study aimed at investigating the manifestation and prevalence of the commonly reported psychosocial reactions in the university students following the onset of COVID-19 pandemic. METHODS: This cross-sectional survey was carried out during April to May, 2020 in the city of Lahore. Based on the interviews and presenting problems of thirty-nine self-referred students to student counselling service center, a list of twenty-seven self-report measure was presented through an online cross-sectional survey of 510 students enrolled in a private institute. The age range of the participants was between 17-26 years (M, 21.86; SD, 2.94). RESULTS: The results showed that the most frequently reported reactions by university students during COVID-19 is restricted daily routine (92%), preoccupation with cleanliness (86%), feeling uncertain about future (85%), feeling bored (84%) and low mood (84%). The least frequently reported reaction was financial crisis (48%). The findings further showed that 18% of the participants had mild, 34% had moderate, 29% severe and 19% very severe level of problems. CONCLUSIONS: The finding revealed that university students have significantly affected by this pandemic which need attention from mental health professionals.

Co-presence of human papillomaviruses and Epstein-Barr virus is linked with advanced tumor stage: a tissue microarray study in head and neck cancer patients.

BACKGROUND: Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), known oncoviruses, can be co-present and cooperate in the initiation and/or progression of human carcinomas, including head and neck. Based on this fact, we recently reported the prevalence of both HPVs and EBV in cervical and breast cancers. METHODS: We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology. RESULTS: The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of the SCC samples; with a significant correlation between the various HPV types and EBV co-incidence (p = 0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoprotein of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. Additionally, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p < 0.05). More importantly, our data revealed that the co-presence of HPV and EBV is strongly correlated with advanced tumor stage (p = 0.035). CONCLUSION: In this study we show that HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of this cooperation.

Co-prevalence of human Papillomaviruses (HPV) and Epstein-Barr virus (EBV) in healthy blood donors from diverse nationalities in Qatar.

BACKGROUND: Infections by both human oncoviruses, human Papillomaviruses (HPV) and Epstein-Barr virus (EBV) are very common in the adult human population and are associated with various malignancies. While HPV is generally transmitted sexually or via skin-to-skin contact, EBV is frequently transmitted by oral secretions, blood transfusions and organ transplants. This study aims to determine the prevalence and circulating genotypes of HPV and EBV in healthy blood donors in Qatar. METHODS: We explored the co-prevalence of high-risk HPVs and EBV in 378 males and only 7 females blood donors of different nationalities (mainly from Qatar, Egypt, Syria, Jordan, Pakistan, and India) residing in Qatar, using polymerase chain reaction (PCR). DNA was extracted from the buffy coat and genotyping was performed using PCR and nested-PCR targeting E6 and E7 as well as LMP-1 of HPV and EBV, respectively. RESULTS: We found that from the total number of 385 cases of healthy blood donors studied, 54.8% and 61% of the samples are HPVs and EBV positive, respectively. Additionally, our data revealed that the co-presence of both high-risk HPVs and EBV is 40.4% of the total samples. More significantly, this study pointed out for the first time that the most frequent high-risk HPV types in Qatar are 59 (54.8%), 31 (53.7%), 52 (49.1%), 51 (48.6%), 58 (47%) and 35 (45.5%), while the most commonly expressed low-risk HPV types are 53 (50.6%), 11 (45.5), 73 (41.7%) and 6 (41.3%), with all the cases showing multiple HPVs infection. CONCLUSION: In this study, we demonstrated for the first time that HPV and EBV are commonly co-present in healthy blood donors in Qatar. On the other hand, it is important to highlight that these oncoviruses can also be co-present in several types of human cancers where they can cooperate in the initiation and/or progression of these cancers. Therefore, more studies regarding the co-presence of these oncoviruses and their interaction are necessary to understand their cooperative role in human diseases.

Elaeagnus angustifolia Plant Extract Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis via HER2 Inactivation and JNK Pathway in HER2-Positive Breast Cancer Cells.

Elaeagnus angustifolia (EA) is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of EA extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous EA extract obtained from the flowers of EA on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that EA extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. EA extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and ß-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, EA extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that EA extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of EA extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that EA extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways.

The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA.

Packaging the mouse mammary tumor virus (MMTV) genomic RNA (gRNA) requires the entire 5' untranslated region (UTR) in conjunction with the first 120 nucleotides of the gag gene. This region includes several palindromic (pal) sequence(s) and stable stem loops (SLs). Among these, stem loop 4 (SL4) adopts a bifurcated structure consisting of three stems, two apical loops, and an internal loop. Pal II, located in one of the apical loops, mediates gRNA dimerization, a process intricately linked to packaging. We thus hypothesized that the bifurcated SL4 structure could constitute the major gRNA packaging determinant. To test this hypothesis, the two apical loops and the flanking sequences forming the bifurcated SL4 were individually mutated. These mutations all had deleterious effects on gRNA packaging and propagation. Next, single and compensatory mutants were designed to destabilize then recreate the bifurcated SL4 structure. A structure-function analysis using bioinformatics predictions and RNA chemical probing revealed that mutations that led to the loss of the SL4 bifurcated structure abrogated RNA packaging and propagation, while compensatory mutations that recreated the native SL4 structure restored RNA packaging and propagation to wild type levels. Altogether, our results demonstrate that SL4 constitutes the principal packaging determinant of MMTV gRNA. Our findings further suggest that SL4 acts as a structural switch that can not only differentiate between RNA for translation versus packaging/dimerization, but its location also allows differentiation between spliced and unspliced RNAs during gRNA encapsidation.

Comparative Evaluation of Foveal Avascular Zone on Two Optical Coherence Tomography Angiography Devices.

SIGNIFICANCE: This study compares foveal avascular zone (FAZ) geometry in healthy eyes as imaged by two commercially available optical coherence tomography angiography (OCTA) devices. Foveal avascular zone measurements are repeatable and reproducible with each OCTA device, but interdevice agreement was poor. We provide conversion factors between devices. PURPOSE: The purpose of this study was to perform comparative evaluation of FAZ geometry in healthy eyes as imaged by two commercially available OCTA devices. METHODS: Ninety-six eyes of 48 healthy subjects were imaged prospectively on each of two OCTA devices (DRI-OCT [Topcon Corporation, Tokyo, Japan]; Cirrus 5000 [Carl Zeiss Meditec Inc., Dublin, CA]). The FAZ was evaluated in the superficial capillary plexus layer of 6 × 6-mm foveal scans by two masked observers. Intraobserver and interobserver agreement was determined using intraclass correlation by using linear mixed models and Bland-Altman plots. K-means clustering was used to provide conversion values between two devices. Foveal avascular zone acircularity was calculated using scans from each device and compared. RESULTS: The intraobserver repeatability for DRI-OCT was 0.95 (95% confidence interval [CI], 0.90 to 0.98) for observer A and 0.92 (95% CI, 0.83 to 0.96) for observer B. Intraobserver repeatability for Cirrus 5000 was 0.988 (95% CI, 0.972 to 0.995) for observer A and 0.993 (95% CI, 0.983 to 0.997) for observer B. The interobserver variability between observers A and B for DRI-OCT was 0.87 (0.73 to 0.94) and for Cirrus 5000 was 0.984 (95% CI, 0.964 to 0.993). Poor interdevice agreement (0.205 [95% CI, -0.202 to 0.554]) was noted, and conversion formulas were devised to convert FAZ area measurements from one device to another. No significant correlation was found when comparing FAZ acircularity indices between devices (P = .39). CONCLUSIONS: Repeatable and reproducible FAZ area measurements were obtained with each respective OCTA device, but interdevice agreement was poor, yet quantifiable and systematic with calculable conversion factors between devices.

SHAPE analysis of the 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA reveals structural elements required for genome dimerization.

Earlier genetic and structural prediction analyses revealed that the packaging determinants of Mason Pfizer monkey virus (MPMV) include two discontinuous core regions at the 5' end of its genomic RNA. RNA secondary structure predictions suggested that these packaging determinants fold into several stem-loops (SLs). To experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), which examines the flexibility of the RNA backbone at each nucleotide position. Our SHAPE data validated several predicted structural motifs, including U5/Gag long-range interactions (LRIs), a stretch of single-stranded purine (ssPurine)-rich region, and a distinctive G-C-rich palindromic (pal) SL. Minimum free-energy structure predictions, phylogenetic, and in silico modeling analyses of different MPMV strains revealed that the U5 and gag sequences involved in the LRIs differ minimally within strains and maintain a very high degree of complementarity. Since the pal SL forms a helix loop containing a canonical "GC" dyad, it may act as a RNA dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Analyses of wild-type and pal mutant RNAs revealed that disruption of pal sequence strongly affected RNA dimerization. However, when in vitro transcribed trans-complementary pal mutants were incubated together showed RNA dimerization was restored authenticating that the pal loop (5'-CGGCCG-3') functions as DIS.

Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV).

BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.

Knowledge, Awareness, and Perception of Common Eye Diseases and Eye Donation Among People Seeking Healthcare in a Tertiary Hospital in Telangana, South India.

Background Globally billions of people have vision impairment (VI) or blindness, and at least half of the VI could have been prevented or has yet to be addressed. With the policies focused exclusively on treating ailments, we need to recognize the need to educate the country's population regarding diseases and their outcomes. This is evident in the poor eye donation rates, as documented by the Eye Bank Association of India (EBAI). The National Programme for Prevention of Blindness (NPCB) also advocates the need for active campaigning to promote eye donations and improve the corneal procurement rate by increasing health awareness. This study aimed to assess the knowledge, awareness, and perception regarding eye diseases and eye donation among the rural population of Telangana, South India. Methods A cross-sectional study involving 150 participants who were randomly selected from non-triaged attendants in the outpatient queue at Mahavir institute of medical sciences (MIMS) was included. Trained enumerators used verbally administered, semi-structured questionnaires on their awareness and knowledge of cataracts, glaucoma, diabetic retinopathy, and night blindness. The Chi-square test was applied to determine the statistical significance of the results obtained from the pre-test and post-test. The significance threshold of the p-value was set at <0.05. Results The population studied belonged to a mean age of 34.98 years. The study included 72 (48%) male and 78 (52%) female subjects, and the majority (48.6%) of them belonged to the age range of 21-30 years. More than 85% of subjects belonged to the middle and lower middle class, and the majority (74.7%) were Hindus by religion. Regarding cataracts, 64 (42.7%) did not know, and 86 (57.3%) had varied perceptions. The awareness regarding glaucoma was the least (88.7%) of all common ocular diseases. The study showed a significant association between knowledge of eye diseases and literacy status plus the population's socioeconomic status (p<0.05 ). A significant association was found to exist between willingness to eye donation and the religion of the study population (p<0.05). Conclusion This study identifies that the awareness regarding various ocular diseases was poor. Moreover, the participants had an alarmingly high misconception regarding different aspects of eye donation. Increasing public awareness is essential to minimize eye diseases, improve eye care, and encourage eye donations.

World Health Organization Versus Diabetes in Pregnancy Study Group India Approaches in the Screening of Gestational Diabetes Among Pregnant Women With Risk Factors: A Study Among Rural Population of Telangana, South India.

Background Gestational diabetes mellitus (GDM) represents a pathological condition wherein pregnant women (PW) suffer from glycemic dysregulation, which predisposes them to an increased risk of developing complications related to pregnancy and childbirth. The most commonly used guidelines to screen for GDM include those provided by the World Health Organization (WHO), the American Congress of Obstetricians and Gynecologists, the Canadian Diabetes Association, and the International Association of Diabetes and Pregnancy Study Group. The Diabetes in Pregnancy Study Group India (DIPSI) guidelines are national-level recommendations to screen for GDM in India. This study aimed to compare the efficacy of DIPSI criteria versus the WHO guidelines in screening for GDM among the rural population of Telangana, South India Methods A total of 300 PW aged 19-35 years with a gestational age of 24-28 weeks attending the antenatal clinic attached to Mahavir Institute of Medical Sciences (MIMS), Vikarabad, Telangana, India were included in the study. The study was approved by the Institutional Ethics Committee of MIMS, and informed consent was obtained from all the participants. Of the 300 subjects included, 75 PW were categorized as at-risk for GDM based on risk factors and were included for further analysis. The data relating to body mass index (BMI), oral glucose tolerance test, and the diagnosis of GDM based on DIPSI and the WHO criteria were collected. Results Out of the 75 PW included in the study, an overall GDM prevalence of 32% was noted among which 20 (26.7%) were diagnosed using the WHO criteria, 12 (16%) by DIPSI criteria, and the remaining 73.3% were non-GDM women. The mean gestational age and BMI among non-GDM and GDM patients were 24.74±4.15 weeks, 22.24±3.60 kg/m2, and 25.70±4.40, 24.48±3.37 kg/m2 (p<0.01), respectively. The activities of glucose at the second hour after a GTT among non-GDM and GDM cases were 113.70±20.4 mg/dL and 128.04±18.6 mg/dL (p=0.004), respectively.  Conclusion DIPSI criteria could identify fewer numbers of GDM women as compared to the WHO criteria. Although the DIPSI criteria are convenient and prescribe less number of interventions, they could possibly miss many cases of GDM. Moreover, PW who remain undiagnosed could, in the future, be at risk of developing diabetes. Based on the study results and because risks should outweigh the benefits, we propose that DIPSI cannot be implemented as a single criterion to screen for GDM among PW in Indian settings.

Fiber-enriched botanicals: A therapeutic tool against certain metabolic ailments.

Plant-based foods are natural sources including vegetables, fruits, cereals and legumes. These foods consist of various types of nutrients in which carbohydrate is the basic component. However, some plant-based diets contain carbohydrates in the form of fiber. The fiber is usually a nondigestible polysaccharide that is not digested in the human body. It is present in the form of soluble or insoluble in different part of foods like peel, bran, pulp and grain. Pectin, beta-glucan, mucilage, psyllium, resistant starch and inulin are soluble fiber, and cellulose, hemicellulose and lignin are insoluble fiber attained from plant foods. The major function enhances immunity by creating gastrointestinal barrier, mucus production, immune cell activity and IgA level. Previous evidences showed that peoples with strong immunity have fewer chances of viral disease. A recent viral disease named COVID-19 spread in the world and millions of peoples died due to this viral disease. Coronavirus mostly attacks humans that suffer with weak immune system. It is due chronic diseases like diabetes and CVD (cardiovascular disease). The current review shows that fiber-containing plant-based foods boost immunity and aid human against COVID-19. The therapeutic role of fiber in the human body is to control the risk of hypertension and diabetes because a high-fiber diet has the ability to lower cholesterol, blood pressure and blood sugar. Fibers aid in GIT (gastrointestinal tract) and prevent constipation because it absorbs water and adds bulk to stool.

Assessment of Breastfeeding, Weaning, and Complementary Feeding Practices Among Women Attending a Tertiary Care Teaching Hospital in South India.

Introduction Infants depend exclusively on mothers' milk for nutrition in their early months of life. However, some infants are given cow/buffalo milk during insufficiency. After six months, the children are supplemented with complementary food, including solid food, to meet the nutritional requirements of a growing infant, a process known as weaning. Therefore, it is important for mothers to have a clear understanding of the nature of food, and the nutritional requirements of the children. This study aimed to understand the knowledge, awareness, and practice of breastfeeding, weaning, and complementary feeding among women. Methods A cross-sectional questionnaire-based observational study was carried out between May and June 2021. The study included 150 women attending the outpatient department of pediatrics attached to Mahavir Institute of Medical Sciences (MIMS), Vikarabad, Telangana, India. After taking the informed consent, the researcher filled out a pre-validated questionnaire based on the subjects' responses. The data regarding socio-demographic details and information regarding knowledge, timing, practices of weaning, knowledge of nutritional requirements, and child feeding practices were collected as a pre-test. An educational briefing of the essentials of child feeding practices, weaning, and dietary requirements was undertaken using chalk and board and audio-visual aids, among others. In the post-test, the knowledge of mothers regarding weaning practices, the importance of weaning, and understanding of the nutritional requirements and their inclusion in a child's diet was assessed. The quantitative data were represented as percentages. The Chi-square test was applied to find out the statistical significance of the results obtained from the study. Results Of the 150 women who participated in the study, the majority belonged to the age group of 18-23 years (66.7%). Most women were illiterate (34%) and only 12% were graduates. More than 70% of the participants belonged to the middle and lower middle class. The majority of participants (96.7%) had carried out exclusive breastfeeding for the first six months, and 63.35% of mothers had initiated weaning their child between the age of 6-12 months. Only 37.4% of mothers started breastfeeding within hours after the delivery. A combination of all foods (36%), rice/wheat (29%), processed food (18.8%), fruits and vegetables (9.2%), and pulses (6.7%) were chosen for weaning. Many felt that eggs and meat supplementation can be done between 12-18 months. Conclusion The knowledge of breastfeeding and best practices of weaning and complementary feeding habits significantly affects the child's growth and overall health. The women in this study had a moderate level of understanding regarding the aspects of breastfeeding, weaning practices, and complementary dietary requirements during weaning.

Polycystic Ovarian Syndrome: Prevalence, Predisposing Factors, and Awareness Among Adolescent and Young Girls of South India.

Introduction Polycystic ovarian syndrome (PCOS) is a leading cause of infertility among women throughout the world. PCOS is an endocrine abnormality that presents as hyperandrogenemia, anovulation, and/or polycystic ovaries. The exact causes of PCOS are not entirely understood. However, PCOS may be hereditary and associated with abnormalities such as high body mass index (BMI) and obesity, among others. This study is carried out to assess the prevalence and awareness among adolescents and young girls belonging to South India. Methods This was a prospective study that included 250 adolescent and young girls aged between 13 and 25 years. Demographic details including age, educational status, and family income were collected from all the participants after obtaining informed consent. BMI was measured in all the participants. A pre-test was conducted to assess the level of awareness followed by a 30-minute informative briefing on PCOS. All participants were asked to fill up a post-briefing questionnaire. The data collected were processed using statistical software SPSS 11.0, and the chi-square test was applied to find out the significance of the results. Results Of the total 250 participants included, the mean age was 16.96 years and most participants (78%) belonged to the age group of 13 to 19 years. Most (78%) of the study participants had normal BMI (18-24.9 kg/m2), 17.6% were underweight (BMI < 18), and 4.4% were overweight (BMI > 25). A PCOS prevalence rate of 6.8% was noted among the study participants. A majority (78.4%) of the study participants were unaware of PCOS, and 6.8% were being treated for PCOS. The source of knowledge of PCOS was majorly teachers (37%), followed by doctors (31.5%), the internet (11%), and friends (7.5%). Lack of information and publicity (63%) were found to be the most significant reason for low levels of awareness. Conclusion PCOS is a common health problem among adolescents and young girls. Most study participants were unaware of the symptoms and management of the condition. Therefore, the disease burden noted in this study does not necessarily depict the real prevalence. Increasing awareness programs will facilitate improved understanding, increased diagnoses, and effective management of PCOS.

Toxicity of Five Plant Volatiles to Adult and Egg Stages of Drosophila suzukii Matsumura (Diptera: Drosophilidae), the Spotted-Wing Drosophila.

The environmental impact of methyl bromide (MB) has resulted in its phase out as an insecticidal fumigant except for critical use exempted categories. Consequently, there is an urgent need to develop an environmentally sustainable MB alternative fumigant. trans-Cinnamaldehyde (TC), benzaldehyde, allyl isothiocyanate (AITC), hexanal, and ethyl formate (EF) are naturally occurring plant volatiles with insecticidal properties. This study assessed the toxicity of these plant volatiles to adult and egg stages of the spotted-wing drosophila (SWD) (Drosophila suzukii Matsumura). The plant volatile treatments had a significant effect on adult SWD mortality. The descending order of toxicity to adult SWD was benzaldehyde > AITC > TC > hexanal > EF at a headspace concentration of 0.50 µL/L air for 24 h. All the volatiles, at a concentration of 4.00 µL/L air, significantly inhibited larval emergence from SWD eggs in artificial diet compared to the control. At a 0.50 µL/L air level, among the volatiles tested, only AITC exhibited 100% inhibition against larval emergence from SWD eggs in blueberry fruits after 24 h exposure. In summary, this study shows that all volatiles tested elicited varying degrees of toxicity toward SWD adults and eggs. However, AITC was the most efficacious volatile and the one with the greatest promise as a post-harvest fumigant for both adult and egg stages of SWD.

Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells via Erk1/Erk2 and ß-Catenin Signaling Pathways.

Breast cancer is a leading cause of death in women around the world. Most breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are co-presented in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and latent membrane protein 1 (LMP1) oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial-mesenchymal transition biomarkers including E-cadherin, ß-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to ß-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progression via Erk1/Erk2 and ß-catenin signaling pathways.

Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo.

Dasatinib is a targeted cancer therapy, while programmed death ligand 1 (PD-L1) inhibitors are a form of immune checkpoint therapy used to treat various types of cancers. Several studies showed the potential efficacy of these drugs in the management of triple-negative breast cancer- an aggressive subtype of breast cancer, which can develop during pregnancy. Nevertheless, side effects of Dasatinib (DA) and PD-L1 drugs during pregnancy, especially in the early stages of embryogenesis are not explored yet. The aim of this study is to assess the individual and combined toxicity of DA and PD-L1 inhibitors during the early stages of embryogenesis and to evaluate their effect(s) on angiogenesis using the chorioallantoic membrane (CAM) model of the embryo. Our results show that embryos die at greater rates after exposure to DA and PD-L1 inhibitors as compared to their matched controls. Moreover, treatment with these drugs significantly inhibits angiogenesis of the CAM. To further elucidate key regulator genes of embryotoxicity induced by the actions of PD-L1 and DA, an RT-PCR analysis was performed for seven target genes that regulate cell proliferation, angiogenesis, and survival (ATF3, FOXA2, MAPRE2, RIPK1, INHBA, SERPINA4, and VEGFC). Our data revealed that these genes are significantly deregulated in the brain, heart, and liver tissues of exposed embryos, compared to matched control tissues. Nevertheless, further studies are necessary to evaluate the effects of these anti breast cancer drugs and elucidate their role during pregnancy.