Clinical and biomarker assessment of frailty in liver transplantation.

PURPOSE OF REVIEW: Liver cirrhosis results in progressive decline, or frailty, which leads to poor outcomes and decreased survival. Multiple biomarkers and clinical assessment tools for quantifying frailty in liver transplant candidates exist, but a universal scoring protocol is lacking. Criteria vary between studies and correlation with patient outcome is not always clear. This review aims to summarize the pertinent biomarkers and assessment tools of frailty in cirrhosis. RECENT FINDINGS: As cirrhosis progresses, the resultant 'frailty' is an inseparable independent predictor of pre and posttransplant mortality. Pro-inflammatory, neuroendocrine, and adipokine factors are dysregulated - leading to paradoxical anorexia and downregulation of orexigenic signals. The resulting catabolic utilization of amino and fatty acids leads to progressive malnutrition and sarcopenia. Both functional and imaging criteria define sarcopenia in cirrhotic patients, and degree of debilitation correlates with mortality. Liver-disease-specific frailty biomarkers and scoring tools are optimal to assess physical dysfunction in cirrhotics to promote early diagnosis and intervention. SUMMARY: Liver cirrhosis and resulting frailty are progressive and portend a poor patient prognosis. A comprehensive, validated algorithm for detecting and quantifying frailty specific to liver disease would allow for standardization and facile application in the clinical setting. Early diagnosis is key for timely intervention and improved patient outcomes.

Clear cell variant of Oral Squamous cell carcinoma.

OBJECTIVE: Among the various histopathological variants of oral squamous cell carcinoma, clear cell variant is a rarity. (1) This report is a compilation of two cases which showed the presence of clear cells. The clear cells were of koilocytic type. Although clear cell variant of squamous cell carcinoma is more common in skin, few cases have been found in oral region also. (2) This variant is considered more aggressive than the others, and hence requires more aggressive treatment protocol. Being rare, the percentage of clear cells determines whether it should be considered as a clear cell variant. The literature has been evaluated for similar cases, and discussed about the clear cells and their origin. An effort has also been made to compile the reported cases of clear cell variant of OSCC.

Plasmodium helical interspersed subtelomeric family-an enigmatic piece of the Plasmodium biology puzzle.

Plasmodium falciparum (Pf) refurbishes the infected erythrocytes by exporting a myriad of parasite proteins to the host cell. A novel exported protein family 'Plasmodium Helical Interspersed Subtelomeric' (PHIST) has gained attention for its significant roles in parasite biology. Here, we have collected and analysed available information on PHIST members to enhance understanding of their functions, varied localization and structure-function correlation. Functional diversity of PHIST proteins is highlighted by their involvement in PfEMP1 (Pf erythrocyte membrane protein 1) expression, trafficking and switching. This family also contributes to cytoadherence, gametocytogenesis, host cell modification and generation of extracellular vesicles. While the PHIST domain forms the hallmark of this family, existence and functions of additional domains (LyMP, TIGR01639) and the MEC motif underscores its diversity further. Since specific PHIST proteins seem to form pairs with PfEMP1 members, we have used in silico tools to predict such potential partners in Pf. This information and our analysis of structural data on a PHIST member provide important insights into their functioning. This review overall enables readers to view the PHIST family comprehensively, while highlighting key knowledge gaps in the field.

Basal cell ameloblastoma: a rare entity expressed in a middle aged female.

OBJECTIVE: Ameloblastoma is a true neoplasm of enamel organ type tissue which does not undergo differentiation to the point of enamel formation. It is a benign, locally invasive tumour of the oral cavity, most commonly affecting the maxilla and the mandible. Histologically there are several variants of ameloblastoma, the basal cell type being the least reported one. In this paper, we are presenting a case of basal cell ameloblastoma of the mandible with a brief review of literature.

Oral submucous fibrosis: an etiological dilemma.

OBJECTIVE: Oral Submucous Fibrosis (OSF), is a well-recognized, oral potentially malignant disorder predominantly affecting the South- Asian countries. OSF causes unique generalized fibrosis of the submucosal oral soft tissues, resulting in marked rigidity of the oral mucosa leading to progressive inability to open the mouth, rigidity of lips and difficulty in protruding the tongue. In this review we have discussed the multifactorial etiology of this potentially malignant disorder, including Chillies, Nutritional Deficiencies, Inducible nitric oxide synthsis (iNOS), genetic and immunological predisposition; and most importantly the role of areca nut and the effect of copper content in it.

Peripheral odontogenic fibroma: a rare gingival neoplasm with clinico-pathological differential diagnosis.

The peripheral odontogenic fibroma (POdF) is a rare gingival neoplasm, characterised by relatively mature collagenous fibrous tissue and varying amounts of odontogenic epithelium. It can be described as a slow growing, firmly attached, solid and smooth gingival mass which may be present asymptomatically for years, which may cause displacement of adjacent teeth. The purpose of this article is to discuss a case of POdF, occurring in the maxillary anterior region, with detailed clinico-pathological differential diagnosis to clarify characteristic features of various gingival overgrowths to enhance easy identification.

An intracellular domain fragment of the p75 neurotrophin receptor (p75(NTR)) enhances tropomyosin receptor kinase A (TrkA) receptor function.

Facilitation of nerve growth factor (NGF) signaling by the p75 neurotrophin receptor (p75(NTR)) is critical for neuronal survival and differentiation. However, the interaction between p75(NTR) and TrkA receptors required for this activity is not understood. Here, we report that a specific 29-amino acid peptide derived from the intracellular domain fragment of p75(NTR) interacts with and potentiates binding of NGF to TrkA-expressing cells, leading to increased neurite outgrowth in sympathetic neurons as a result of enhanced Erk1/2 and Akt signaling. An endogenous intracellular domain fragment of p75(NTR) (p75(ICD)) containing these 29 amino acids is produced by regulated proteolysis of the full-length receptor. We demonstrate that generation of this fragment is a requirement for p75(NTR) to facilitate TrkA signaling in neurons and propose that the juxtamembrane region of p75(ICD) acts to cause a conformational change within the extracellular domain of TrkA. This finding provides new insight into the mechanism by which p75(NTR) and TrkA interact to enhance neurotrophic signaling.

Identification of the pattern of copper as an etiological factor in oral submucous fibrosis: a cytological study.

UNLABELLED: Oral Submucous Fibrosis (OSF) is a well-recognized, potentially malignant disorder causing generalized fibrosis of the submucosal oral soft tissues. Though this disease is believed to be multi-factorial, areca nut chewing has emerged as the most important causative factor for OSF. Areca nut is known to have high levels of copper, which is believed to cause lysyl oxidase associated fibrosis. AIM: To evaluate the pattern of copper in buccal mucosal cells of OSF patients, areca nut chewers and normal healthy individuals and to elicit the etiology of copper in OSF. MATERIALS AND METHODS: Patients were divided into three groups each comprising of 20 individuals- Healthy individuals (Group I); areca nut chewers without OSF (Group II); histopathologically confirmed OSF (Group Ill). The cytological smears made from each patient were stained with rhodanine stain for copper and evaluated for the qualitative and quantitative parameters of copper by using specific grading criteria. RESULTS: Quantitative estimation of copper content showed a marked variation in the mean values. Mean value of group I was 0.11 ± 0.39; group II was 1.09 ± 0.81 and group III was 2.34 ± 0.74 (p<0.001). Mean values for qualitative estimation of copper were - 0.01 ± 0.36 for group I, 1.08 ± 0.82 for group II and 2.39 ± 0.72 for group III (p<0.001). Chi square analysis was used to assess the percentage distribution of copper granules. This revealed that the colour intensity and the number of granules were seen to maximum in OSF patients, areca nut chewers without OSF having intermediated values and normal healthy individuals having the least values. CONCLUSION: An evident increase in the copper staining in group III individuals as compared to group I and group II was well appreciated. Increased copper levels in the local environment of the oral cavity indicates its role in lysyl oxidase associated submucosal fibrosis.

Heel Pain Management in Haglund's Deformity Targeting Sural Nerve Branches under Ultrasound Guidance: Case Report.

Introduction: Haglund's deformity is an abnormality of the bone and soft tissue of the foot, also known as retrocalcaneal exostosis, Mulholland deformity, and "pump bump". The etiology is not well known. Probable causes include a tight Achilles tendon, a high arch of the foot, and hereditary. The clinical features consist of pain at the posterior aspect of the heel which is predominantly present when the patient begins to walk after a period of rest or inactivity. Case Report: We report a case of a 60-year-old teacher with left heel pain for 3 years, unable to stand or walk for more than 15 min due to pain. We diagnosed him as a case of Haglund's deformity and treated him with ultrasound-guided injections targeting the superficial branches of the sural nerve. This case report illustrates a rarely described modality for the management of heel pain due to Haglund's deformity. Targeting superficial branches of the Sural nerve under ultrasound guidance can act as a superior treatment modality for the management of heel pain due to Haglund's deformity. Conclusion: Haglund's deformity is a cause of pain in the hindfoot that should be taken into account in the differential diagnosis of any patient presenting with heel pain. Ultrasonography has proved to be an important cost-effective tool in the diagnosis and management of various ankle pathologies like Haglund's deformity, thereby reducing the sole dependence on surgical management. Targeting the superficial (cutaneous) branches of the sural nerve can give satisfactory long-term relief of heel pain in patients with Haglund deformity.

Challenging Case: New-Onset Hallucinations and Developmental Regression in a Child with Autism Spectrum Disorder.

CASE: Nick is a 5-year-old boy who began displaying self-stimulating behaviors and decreased social interactions shortly before turning 3 years. At the age of 3.5 years, he was diagnosed with autism spectrum disorder by a local developmental-behavioral pediatrician. His parents recall that the physician described Nick to be "high functioning" and encouraged them to expect that he would attend college and live independently as an adult. Upon receiving the diagnosis, intervention was initiated using an applied behavioral analysis (ABA) approach. With this intervention, he demonstrated initial gains in the use of complex language and improved social interactions.Concerns regarding suspected psychosis emerged just before starting kindergarten when Nick began experiencing ego-dystonic visual and auditory hallucinations. Initially, Nick verbally responded to the hallucinations and vividly described what he was experiencing. Shortly after the onset of these hallucinations, Nick experienced a significant decrease in the frequency and complexity of his expressive language and became more withdrawn. Over time, his hallucinations intensified, and his parents became increasingly fearful for his safety. Various antipsychotic and mood-stabilizing medications, steroids, and immunotherapy have been trialed with limited improvement of his symptoms.An extensive medical evaluation yielded the following:1. Magnetic resonance imaging of the brain: dilated perivascular spaces.2. Urine organic acids: ketosis and increased lactic acid.3. Antinuclear antibody: minimally positive.4. Vitamin B12: elevated.All other studies, including lumbar puncture, electroencephalogram (awake and asleep), genetic studies (chromosomal microarray, fragile X testing, and whole exome sequencing), metabolic studies, inflammatory markers, and thyroid panel, were negative/normal.Nick is enrolled in a special education classroom within a school that utilizes an ABA-based approach for all students. As part of his educational programming, he receives 25 hours of ABA in a 1:1 setting, 2 hours of speech therapy, 3 hours of occupational therapy, 1 hour of physical therapy, and 30 minutes of music therapy weekly. Current concerns include significant head-banging and thrashing before falling asleep, hyperactivity, unsafe behaviors (e.g., banging on windows, climbing high to reach desired items), aggression toward caregivers, limited ability to complete self-care tasks (e.g., personal hygiene, toileting), significant decline in expressive language, and continued response to internal stimuli.Nick's parents now present to a multidisciplinary center seeking guidance regarding additional therapies/interventions to assist in management of his current developmental and behavioral challenges as well as information regarding his expected developmental trajectory as he reaches adulthood.

Perceptions of Individuals with Autism Spectrum Disorder on How Health Care Providers Address Sexual Health.

OBJECTIVE: Medical providers report barriers that prevent them from discussing sexual health with patients with autism spectrum disorder (ASD). No investigations have examined the perspectives of adults with ASD about their sexual health care experiences. METHODS: Twenty-five verbal young adults diagnosed with ASD and 40 young adults without ASD participated. An 8-item self-report survey assessed frequency of health care visits, age when sexual health was first discussed, and frequency/content of discussions with providers. RESULTS: The likelihood of discussing sexual health topics did not differ by group, χ2s < 3.25; ps > 0.07, except sexual victimization, which the ASD group reported having discussed less than the non-ASD group (32 vs 9%), χ2 (1, N = 57) = 4.36, p = 0.04. Groups did not differ in their reported comfort level discussing sex/sexual health, having a primary care provider, or frequency of visits. The non-ASD group was significantly more likely to have received sexual health counseling (81%) than ASD group (52%), χ2 (1, N = 58) = 5.33, p = 0.02. Participants in both groups reported having received sexual health information from similar sources except the ASD group was more likely to receive information from parents than the non-ASD group (68% vs 30%), χ2 (1, N = 65) = 8.99, p = 0.003. CONCLUSION: Participants in the ASD and non-ASD groups reported similar comfort levels with sexual health discussions and access to health providers. Yet, the ASD group received less counseling related to sexual health-particularly sexual victimization screening-suggesting that critical information may be missing. Future studies should determine how to help providers overcome barriers to providing young adults with ASD sexual health aligned with their needs.

Exploring ncRNAs in epilepsy: From oxidative stress regulation to therapy.

Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers.

Field cancerization: concept and clinical implications in head and neck squamous cell carcinoma.

Cancer begins with multiple cumulative epigenetic and genetic alterations that sequentially transform a cell or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remains in the organ, demonstrating the concept of field cancerization. The concept of "field cancerization" was first introduced by Slaughter et al in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. With present technological advancement and carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumor-specific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in head and neck cancer and its possible utility in early detection, tumor progression and clinical significance.

Hyperphagia and Down Syndrome.

CASE: A.Z. is a 14-year-old young boy with Down syndrome and intellectual disability. As a baby and toddler, A.Z. struggled with swallowing dysfunction and recurrent aspiration, which improved by the time he was school aged. At the age of 2 years, his body mass index (BMI) was 95.98% (Z score 1.75). During his early school-age years, A.Z. began eating a wider variety of foods. As he grew taller and remained active, his BMI improved briefly during this time. Between ages 10 and 12 years, concerns regarding increased appetite and excessive weight gain emerged. His BMI increased from 82.56% (Z score 0.94) to 98.27% (Z score 2.11) during this time. He became insatiable; he ate when he was happy, upset, or bored. He had a compulsive need to eat all day, which escalated while staying home during the COVID pandemic. Despite having complete meals and a variety of snacks, he overate and sought out food and snacks, no matter the time of the day. Food also became a source of contention and a trigger for verbally and physically aggressive behavior when parents attempted to restrict food intake. Behavioral therapy was recommended to address his eating patterns as a part of his behavioral management plan.Over time, many strategies were used, including a token economy reward system, setting firm limits around snacking and meals, creating a food schedule with times and forced choice options, use of coping skill training, a feelings thermometer, and communication supports. These interventions had moderate intermittent success; however, overeating and consequent power struggles continued to be the major challenge reported by the family.He was started on a long-acting stimulant medication daily, intended to address impulsive and aggressive behaviors, and with potential benefit of appetite reduction. However, although there were some improvements in behavior, there was little to no effect noted on his appetite. Of note, he was diagnosed with celiac disease and severe obstructive sleep apnea at this time. A.Z. remained compliant with his gluten-free diet despite the challenges he experienced with food seeking and portion control. Overall, despite making excellent progress in behavioral regulation and performing particularly well in structured settings outside the home (i.e., school or summer camp), A.Z. continued to binge eat and seek out food with his most recent BMI at 98.62% (Z score 2.20).CASE 2: C.J. is a 9-year-old boy with Down syndrome and intellectual disability. As a toddler, C.J. had a brief period of time in which he was noted to overeat or not sense when he was full and subsequently gag or vomit after meals. At age 5 to 6 years, C.J. began demonstrating a more voracious appetite and increased weight gain; his BMI was 99.43% (Z score 2.53). Behavioral strategies, such as food schedules with forced choice options, were recommended. C.J. responded with increased dysregulation to the limit setting. An additional trigger for C.J. was the irregular visitation schedule with his father. He also hid and hoarded food; for example, he often ate food and hid the wrappers in the trash. Locking the refrigerator and cabinets resulted in binging on whatever he could find, such as ketchup packets. If C.J. wanted food during a time outside of his schedule, he was provided a list of alternative activities to choose from. It was recommended that his parent portion foods for him and set clear expectations of eating in the kitchen alone.C.J. was trialed on a short-acting alpha-agonist agent for 1 year to help address some of his behavioral challenges. Despite initial improvement on this regimen, behavioral challenges reemerged, and his eating behaviors worsened, so the medication was stopped. After stopping the medication, C.J. responded well to the limit setting, including regulating his own portion sizes and using a portion control plate. The family believed that the short-acting alpha-agonist worsened his food-seeking behaviors, although this was not clinically apparent. Despite having continued affinity for certain foods and snacks, C.J. was no longer binge eating or hoarding and hiding food. His most recent BMI remained elevated at 99.24% (Z score 2.43).

Deep learning for face mask detection: a survey.

The Coronavirus Disease (Covid-19) was declared as a pandemic by WHO (World Health Organization) on 11 March 2020, and it is still currently going on, thereby impacting tremendously the whole world. As of September 2021, more than 220 million cases and 4.56 million deaths have been confirmed, which is a vast number and a significant threat to humanity. Although, As of 6 September 2021, a total of 5,352,927,296 vaccine doses have been administered, still many people worldwide are not fully vaccinated yet. As stated by WHO, "Masks" should be used as one of the measures to restrain the transmission of this virus. So, to reduce the infection, one has to cover their face, and to detect whether a person's face is covered with a mask or not, a "Face mask detection system" is needed. Face Mask Detection falls under the category of "Object Detection," which is one of the sub-domains of Computer Vision and Image Processing. Object Detection consists of both "Image Classification" and "Image Localization". Deep learning is a subset of Machine learning which, in turn, is a subset of Artificial intelligence that is widely being used to detect face masks; even some people are using hybrid approaches to make the most use of it and to build an efficient "Face mask detection system". In this paper, the main aim is to review all the research that has been done till now on this topic, various datasets and Techniques used, and their performances followed by limitations and improvements. As a result, the purpose of this study is to give a broader perspective to a researcher to identify patterns and trends in Face mask detection (Object Detection) within the framework of covid-19.

Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

Psychological Problems Related to Infertility.

Infertility is a problem of great significance among millions of couples. In our society, to have a child means living a fulfilled life. Thus, couples who cannot do so feel barren and incomplete. Therefore, infertility is more than just a medical problem. It affects all aspects of life, the most important being mental health. For many years, a person's mental health has been overlooked, but in the past few years, it has gained importance that mental health is as significant as physical health, which has also been stated in the WHO definition of health. This article discusses the mental toll that infertility takes on a person's life. A person may experience a myriad of psychological problems, of which stress for extended periods is one. Furthermore, it may cause feelings of guilt, emptiness, anxiety, and depression. The article mainly focuses on the need for counseling for couples dealing with infertility and under treatment because of the long waiting periods accompanying it. Although both men and women can contribute to infertility in India, women are exclusively held responsible, leading to more significant stress while undergoing treatment. The paper also provides an overview of infertility, the factors responsible, and the treatments currently available. Various studies have shown that delivering psychological support through psychiatric clinical specialists may accentuate the results of IVF (In-vitro fertilization) and ART (Assisted Reproductive Technology). This review sheds light on the effects of infertility on quality of life and how it can be prevented or reduced through psychotherapy.

Dihydrofolate reductase inhibitors: patent landscape and phases of clinical development (2001-2021).

INTRODUCTION: Dihydrofolate reductase (DHFR) plays an important role in the biosynthesis of amino acid and folic acid. It participates by reducing dihydrofolate to tetrahydrofolate, in the presence of nicotinamide dinucleotide phosphate cofactor, and has been verified by various clinical studies to use DHFR as a target for the treatment of cancer and various bacterial infections. AREA COVERED: In this review, we have disclosed patents of synthetics and natural DHFR inhibitors with diaminopyrimidine and quinazoline nucleus from 2001. Additionally, this review highlights the clinical progression of numerous DHFR inhibitors received from the last five years. EXPERT OPINION: From 2001 to 2021, numerous active chemical scaffolds have been introduced and are exposed as lead candidates that have entered clinical trials as potent DHFR inhibitors. Moreover, researchers have paid considerable attention to the development of a new class of DHFR inhibitors with higher selectivity and potency. This development includes synthesis of synthetic as well as natural compounds that are potent DHFR inhibitors. On the basis of literature review, we can anticipate that there are a huge number of novel active molecules available for the future that could possess superior abilities to target this enzyme with a profound pharmacological profile.

Cholinergic basal forebrain degeneration due to sleep-disordered breathing exacerbates pathology in a mouse model of Alzheimer's disease.

Although epidemiological studies indicate that sleep-disordered breathing (SDB) such as obstructive sleep apnea is a strong risk factor for the development of Alzheimer's disease (AD), the mechanisms of the risk remain unclear. Here we developed a method of modeling SDB in mice that replicates key features of the human condition: altered breathing during sleep, sleep disruption, moderate hypoxemia, and cognitive impairment. When we induced SDB in a familial AD model, the mice displayed exacerbation of cognitive impairment and the pathological features of AD, including increased levels of amyloid-beta and inflammatory markers, as well as selective degeneration of cholinergic basal forebrain neurons. These pathological features were not induced by chronic hypoxia or sleep disruption alone. Our results also revealed that the cholinergic neurodegeneration was mediated by the accumulation of nuclear hypoxia inducible factor 1 alpha. Furthermore, restoring blood oxygen levels during sleep to prevent hypoxia prevented the pathological changes induced by the SDB. These findings suggest a signaling mechanism whereby SDB induces cholinergic basal forebrain degeneration.

Intolerance of sexy peers: intrasexual competition among women.

Intrasexual competition among males of different species, including humans, is well documented. Among females, far less is known. Recent nonexperimental studies suggest that women are intolerant of attractive females and use indirect aggression to derogate potential rivals. In Study 1, an experimental design was used to test the evolutionary-based hypothesis that women would be intolerant of sexy women and would censure those who seem to make sex too readily available. Results provide strong empirical support for intrasexual competition among women. Using independent raters, blind to condition, we found that almost all women were rated as reacting negatively ("bitchy") to an attractive female confederate when she was dressed in a sexually provocative manner. In contrast, when she was dressed conservatively, the same confederate was barely noticed by the participants. In Study 2, an experimental design was used to assess whether the sexy female confederate from Study 1 was viewed as a sexual rival by women. Results indicated that as hypothesized, women did not want to introduce her to their boyfriend, allow him to spend time alone with her, or be friends with her. Findings from both studies are discussed in terms of evolutionary theory.