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Background: Viral bronchiolitis is a common condition and a leading cause of hospitali-zation in young children. Objective: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. Methods: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR “respiratory syncytial virus infection”. The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observation-al studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. Results: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young chil-dren. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagno-sis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effec-tive. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramus-cularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. Conclusions: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

Although Western medicine and ideas about atopic dermatitis (AD) have become popular in many Asian countries, local beliefs about the disease and its treatment often prevail. The multi- racial background of these countries as well as the influence of the diverse religions (such as Taoism and Ramadan) in these regions often lead to diverse belief systems about the causes of AD (such as the Chi concept, also known as the balance of yin and yang) and the types of treatment (e.g. herbal remedies, topical versus concoctions, and decoctions). In addition, many of the cultural practices are preserved among the Southeast Asian minorities residing in the United Kingdom and North America. Eastern treatments typically take a holistic approach to AD and emphasize the psychosomatic component of the disorder. This overview provides a summary of the difference between Conventional, Complementary, Alternative, and Integrative Medicine in terms of epidemiology, aetiology, therapy, and prognosis in children with AD. There are a number of similarities in genetic and environmental factors in epidemiology and aetiology; however, differences exist in terms of the concept of management. Complementary and alternative medicine, traditional Chinese medicine, and integrative medicine usage are not only prevalent among the Asian population but are also becoming more popular and accepted in Western societies.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8-12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Memory is better for emotional rather than neutral events or materials (emotional enhancement of memory; EEM). Evidence suggests that this memory benefit remains intact in schizophrenia, but conflicting findings present the need for further research to understand how and when this process occurs. Here, we examine whether different encoding methods for learning emotional faces may result in different EEM patterns in those with schizophrenia spectrum disorders (SSD). A patient group (n = 28) and healthy comparisons (n = 29) encoded faces in two conditions that manipulated attentional focus to promote direct (emotion judgements) or indirect (sex discrimination) processing of emotional content. Based on literature in schizophrenia showing selective emotion perception deficits on tasks of direct processing but relatively intact emotion perception on indirect processing tasks, we hypothesized that patients would show greater EEM effects when faces were encoded indirectly. This hypothesis was not supported, and the patient group instead showed a similar intact EEM for angry and fearful faces to healthy comparisons in both encoding conditions. Further, using the Remember/Know paradigm, we demonstrated that the EEM in SSD appears selective to recollection-based memory, which helps to explain inconsistencies in past literature that has not differentiated between recognition domains. These findings have important implications for improving emotional memory and functional outcomes in SSD; future research should establish how the EEM for facial expressions may relate to social functioning.

Background: Childhood obesity is an important and serious public health problem worldwide. Objective: This article aims to familiarize physicians with the evaluation, management, and prevention of childhood. Methods: A PubMed search was conducted in May 2021 in Clinical Queries using the key terms "obesity" OR “obese”. The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to English literature and children. The information retrieved from the above search was used in the compilation of the present article. Results: Most obese children have exogenous obesity characterized by a growth rate for height above the 50th percentile, normal intelligence, normal genitalia, and lack of historical or physical evidence of an endocrine abnormality or a congenital syndrome. Obese children are at risk for dyslipidemia, hypertension, diabetes mellitus, non-alcoholic fatty liver disease, obstructive sleep apnea, psychosocial disturbances, impaired quality of life, and shorter life expectancy. The multitude of serious comorbidities necessitates effective treatment modalities. Dietary modification, therapeutic exercise, and behavioral modification are the fundamentals of treatment. Pharmacotherapy and/or bariatric surgery should be considered for obese individuals who do not respond to the above measures and suffer from a serious comorbid condition. Conclusion: Childhood obesity, once established, is often refractory to treatment. Most treatment programs lead to a brief period of weight loss followed by rapid re-accumulation of the lost weight after termination of therapy. As such, preventive activity is the key to solve the problem of childhood obesity. Childhood obesity can be prevented by promoting healthy diet, regular physical activity, and lifestyle modification. Parents should be encouraged to become involved in school and community programs that improve nutritional status and physical activity in their children.

Background Post-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects Objective/hypothesis To test the use of ECT to disrupt the reconsolidation of traumatic memories as a potential treatment for PTSD Methods Participants were adults from the civilian population and were referred for ECT treatment for severe depression with comorbid PTSD symptoms. Twenty-eight participants were randomly assigned to reactivation of a traumatic or non-traumatic memory using audio script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included a comparison of the change in heart rate while listening to the script Results Twenty-five female patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time Conclusions ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory reactivation. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04027452 . Identifier NCT04027452.

Background: Sleep terrors are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made. Objective: To familiarize physicians with the clinical manifestations, diagnosis, and management of children with sleep terrors. Methods: A PubMed search was completed in Clinical Queries using the key terms " sleep terrors" OR " night terrors". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Results: It is estimated that sleep terrors occur in 1 to 6.5% of children 1 to 12 years of age. Sleep terrors typically occur in children between 4 and 12 years of age, with a peak between 5 and 7 years of age. The exact etiology is not known. Developmental, environmental, organic, psychological, and genetic factors have been identified as a potential cause of sleep terrors. Sleep terrors tend to occur within the first three hours of the major sleep episode, during arousal from stage three or four non-rapid eye movement (NREM) sleep. In a typical attack, the child awakens abruptly from sleep, sits upright in bed or jumps out of bed, screams in terror and intense fear, is panicky, and has a frightened expression. The child is confused and incoherent: verbalization is generally present but disorganized. Autonomic hyperactivity is manifested by tachycardia, tachypnea, diaphoresis, flushed face, dilated pupils, agitation, tremulousness, and increased muscle tone. The child is difficult to arouse and console and may express feelings of anxiety or doom. In the majority of cases, the patient does not awaken fully and settles back to quiet and deep sleep. There is retrograde amnesia for the attack the following morning. Attempts to interrupt a sleep terror episode should be avoided. As sleep deprivation can predispose to sleep terrors, it is important that the child has good sleep hygiene and an appropriate sleeping environment. Medical intervention is usually not necessary, but clonazepam may be considered on a short-term basis at bedtime if sleep terrors are frequent and severe or are associated with functional impairment, such as fatigue, daytime sleepiness, and distress. Anticipatory awakening, performed approximately half an hour before the child is most likely to experience a sleep terror episode, is often effective for the treatment of frequently occurring sleep terrors. Conclusion: Most children outgrow the disorder by late adolescence. In the majority of cases, there is no specific treatment other than reassurance and parental education. Underlying conditions, however, should be treated if possible and precipitating factors should be avoided.

Background :Onychomycosis is a common fungal infection of the nail.Objective:The study aimed to provide an update on the evaluation, diagnosis, and treatment of onychomycosis.Methods:A PubMed search was completed in Clinical Queries using the key term “onychomycosis”. The search was conducted in May 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. The search was restricted to English literature. Patents were searched using the key term “onychomycosis” in www.freepatentsonline.com.Results :Onychomycosis is a fungal infection of the nail unit. Approximately 90% of toenail and 75% of fingernail onychomycosis are caused by dermatophytes, notably Trichophyton mentagrophytes and Trichophyton rubrum. Clinical manifestations include discoloration of the nail, subungual hyperkeratosis, onycholysis, and onychauxis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wet-mount preparation, histopathologic examination of the trimmed affected nail plate with a periodic-acid-Schiff stain, fungal culture, or polymerase chain reaction assays. Laboratory confirmation of onychomycosis before beginning a treatment regimen should be considered. Currently, oral terbinafine is the treatment of choice, followed by oral itraconazole. In general, topical monotherapy can be considered for mild to moderate onychomycosis and is a therapeutic option when oral antifungal agents are contraindicated or cannot be tolerated. Recent patents related to the management of onychomycosis are also discussed.Conclusion:Oral antifungal therapies are effective, but significant adverse effects limit their use. Although topical antifungal therapies have minimal adverse events, they are less effective than oral antifungal therapies, due to poor nail penetration. Therefore, there is a need for exploring more effective and/or alternative treatment modalities for the treatment of onychomycosis which are safer and more effective.

The glucocorticoid receptor (GR) forms a protein complex with FKBP51 that is increased in post-traumatic stress disorder (PTSD) and by fear conditioned learning. Disrupting the GR-FKBP51 complex with a synthetic peptide can block the storage or retrieval of fear conditioned memories, which could be a novel approach to the alleviate fear associated memory in PTSD. However, a potential unacceptable side effect could be the impairment of other types of memory. Thus, we investigated the effect of disrupting the GR-FKBP51 complex on recognition memory using the novel object and displaced object recognition tasks, spatial memory in the Morris water maze, and on social interaction in Crawley's three-chamber social interaction test. We did not observe adverse effects on these other types of memory and conclude that the GR-FKBP51 interaction remains a promising target for treating psychiatric disorders characterized by unwanted aversive memories such as in PTSD.

Background: Giardiasis is an important cause of waterborne and foodborne diarrhea, daycare center outbreaks, and traveler's diarrhea. Objective: The study aimed to provide an update on the evaluation, diagnosis, and treatment of giardiasis. Methods: A PubMed search was completed in Clinical Queries using the key terms “giardiasis”, "Giardia lamblia", "Giardia duodenalis" and "Giardia intestinalis". The search strategy included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. Patents were searched using the key term “giardiasis” from www.freepatentsonline.com. Results: Giardiasis is caused by the protozoan parasite Giardia lamblia. The parasite is transmitted by the fecal-oral route, frequently through ingestion of contaminated water and food or person-to person transmission. Risk factors for infection include children in day-care settings, child-care workers, institutionalized individuals, travelers in endemic areas, ingestion of contaminated or recreational water, immunodeficiency, cystic fibrosis, and oral-anal sex. Approximately 50 to 75% of infected children are asymptomatic. Other children present acute or chronic diarrhea. Direct fluorescent antibody tests that detect intact organisms, enzyme immunoassays that detect soluble antigens, and multiplex real-time polymerase chain reaction assays that detect specific genes of the parasite in stool samples have improved sensitivity and specificity compared with microscopic examination of stool specimens for the detection of Giardia trophozoites or cysts. Drugs used in the treatment of symptomatic giardiasis are reviewed in this study. Moreover, recent patents related to the management of giardiasis are also discussed. Conclusion: Metronidazole, tinidazole, and nitazoxanide are drugs of choice. Resistance to common antigiardial drugs has increased in recent years, therefore, the search for new molecular targets for antigiardial drugs is urgently needed. In general, treatment of asymptomatic carriers is not recommended. Purification of water supply is an important preventive measure.

For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples.Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment.Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands.Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia.

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR–NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR–NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications. Supplementary Information The online version contains supplementary material available at 10.1186/s13041-021-00817-3.

Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit its widespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated two to three times per week with high-frequency MST (i.e., 100 Hz) (N = 24), medium frequency MST (i.e., 60 or 50 Hz) (N = 26), or low-frequency MST (i.e., 25 Hz MST) (N = 36) using 100% stimulator output. One hundred and forty patients were screened; 86 patients with MDD received a minimum of eight treatments and were deemed to have an adequate course of MST; and 47 completed the trial per protocol, either achieving remission (i.e., 24-item Hamilton Rating Scale for Depression score 60% at two consecutive assessments; n = 17) or received a maximum of 24 sessions (n = 30). High-frequency (100 Hz) MST produced the highest remission rate (33.3%). Performance on most cognitive measures remained stable, with the exception of significantly worsened recall consistency of autobiographical information and significantly improved brief visuospatial memory task performance. Under open conditions, MST led to clinically meaningful reduction in depressive symptoms in patients with MDD and produced minimal cognitive impairment. Future studies should compare MST and ECT under double-blind randomized condition.

Background: Urinary Tract Infection (UTI) is a common infection in children. Prompt diagnosis and appropriate treatment are very important to reduce the morbidity associated with this condition. Objective: To provide an update on the evaluation, diagnosis, and treatment of urinary tract infection in children. Methods: A PubMed search was completed in clinical queries using the key terms “urinary tract infection”, "pyelonephritis" OR "cystitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature and the pediatric age group. Patents were searched using the key terms “urinary tract infection” "pyelonephritis" OR "cystitis" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. Results: Escherichia coli accounts for 80 to 90% of UTI in children. The symptoms and signs are nonspecific throughout infancy. Unexplained fever is the most common symptom of UTI during the first two years of life. After the second year of life, symptoms and signs of pyelonephritis include fever, chills, rigor, flank pain, and costovertebral angle tenderness. Lower tract symptoms and signs include suprapubic pain, dysuria, urinary frequency, urgency, cloudy urine, malodorous urine, and suprapubic tenderness. A urinalysis and urine culture should be performed when UTI is suspected. In the work-up of children with UTI, physicians must judiciously utilize imaging studies to minimize exposure of children to radiation. While waiting for the culture results, prompt antibiotic therapy is indicated for symptomatic UTI based on clinical findings and positive urinalysis to eradicate the infection and improve clinical outcome. The choice of antibiotics should take into consideration local data on antibiotic resistance patterns. Recent patents related to the management of UTI are discussed. Conclusion: Currently, a second or third generation cephalosporin and amoxicillin-clavulanate are drugs of choice in the treatment of acute uncomplicated UTI. Parenteral antibiotic therapy is recommended for infants ≤ 2 months and any child who is toxic-looking, hemodynamically unstable, immunocompromised, unable to tolerate oral medication, or not responding to oral medication. A combination of intravenous ampicillin and intravenous/intramuscular gentamycin or a third-generation cephalosporin can be used in those situations. Routine antimicrobial prophylaxis is rarely justified, but continuous antimicrobial prophylaxis should be considered for children with frequent febrile UTI.

Background:Breath-holding spells are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made.Objective:To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of children with breath-holding spells.Methods:A PubMed search was completed in Clinical Queries using the key term "breath-holding spells". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.Results:Breath-holding spells affect 0.1 to 4.6% of otherwise healthy young children. The onset is usually between 6 and 18 months of age. The etiopathogenesis is likely multifactorial and includes autonomic nervous system dysregulation, vagally-mediated cardiac inhibition, delayed myelination of the brain stem, and iron deficiency anemia. Breath-holding spells may be cyanotic or pallid. The former are usually precipitated by anger or frustration while the latter are more often precipitated by pain or fear. In the cyanotic type, the child usually emits a short, loud cry, which leads to a sudden involuntary holding of the breath in forced expiration. The child becomes cyanosed, rigid or limp, followed by a transient loss of consciousness, and a long-awaited inspiration and resolution of the spell. In the pallid type, crying may be minimal or “silent”. The apneic period in the pallid type is briefer than that in the cyanotic type prior to the loss of consciousness and posture. The episode in the pallid type then proceeds in the same manner as a cyanotic spell except that the child in the pallid type develops pallor rather than cyanosis. In both types, the entire episode lasts approximately 10 to 60 seconds. The spells usually disappear spontaneously by 5 years of age.Conclusion:Although breath-holding spells are benign, they can be quite distressing to the parents. Confident reassurance and frank explanation are the cornerstones of treatment. Underlying cause, if present, should be treated. Interventions beyond iron supplementation may be considered for children with severe and frequent breath-holding spells which have a strong impact on the lifestyle of both the child and family.

Importance: Five-year survival rates in patients undergoing vitrectomy for diabetic retinopathy (DR) vary from 68% to 95%. No study has been conducted in an Australian population. Background: We aimed to determine the survival rates of patients undergoing diabetic vitrectomy in an Australian population. Design: Retrospective audit, tertiary centre hospitals and private practices. Participants: All individuals in South Australia and the Northern Territory who underwent their first vitrectomy for diabetic complications between January 1, 2007 and December 31, 2011. Methods: An audit of all eligible participants has been completed previously. Survival status as of July 6, 2018 and cause of death were obtained using SA/NT DataLink. Kaplan-Meier survival curves and multivariate cox-regressions were used to analyse survival rates and identify risk factors for mortality. Main Outcome Measures: Five-, seven- and nine-year survival rates. Results: The 5-, 7- and 9-year survival rates were 84.4%, 77.9% and 74.7%, respectively. The most common cause of death was cardiovascular disease. Associated with increased mortality independent of age were Indigenous ethnicity (HR = 2.04, 95% confidence interval [CI]: 1.17-3.57, P = 0.012), chronic renal failure (HR = 1.76, 95% CI: 1.07-2.89, P = 0.026) and renal failure requiring dialysis (HR = 2.32, 95% CI: 1.25-4.32, P = 0.008). Conclusions and Relevance: Long-term survival rates after diabetic vitrectomy in Australia are similar to rates reported in other populations. Indigenous ethnicity and chronic renal failure were the most significant factors associated with long-term mortality. This information can guide allocation of future resources to improve the prognosis of these high risk groups.

Objective While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human. Methods Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals. Results Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission. Conclusions The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation. Significance These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.

The COVID-19 Pandemic sweeping the globe has cost more than lives and livelihoods. It has rendered a heavy blow to the already shaking America’s global leadership established after World War II. Instead of coordinating with its allies and international organizations to fight the common enemy, the Trump administration focused the bulk of its efforts on blaming China and the World Health Organization (WHO). Overwhelmed by the virus and doing a poor job of protecting its citizens, the US set a bad example for the world and offered no leadership to the rest of the world. The world has come to the post-American order. This Chapter argues that while US has failed to control the COVID-19 and created a vacuum on global leadership China was not yet ready to assume comprehensive leadership role by providing necessary public goods. China's good will was greatly undermined by politicians and public opinions in the West. Nevertheless China is a fast learner and it will play an increasingly important role in Global leadership.

Background: Juvenile dermatomyositis is the most common inflammatory myopathy in the pediatric age group and a major cause of mortality and morbidity in individuals with childhood rheumatic diseases. Mounting evidence suggests that early diagnosis and timely aggressive treatment are associated with better outcomes. Objective: The purpose of this article is to provide readers with an update on the evaluation, diagnosis, and the treatment of juvenile dermatomyositis. Methods: A PubMed search was performed in Clinical Queries using the key term “juvenile dermatomyositis” in the search engine. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Results: Juvenile dermatomyositis is a chronic autoimmune inflammatory condition characterized by systemic capillary vasculopathy that primarily affects the skin and muscles with possible involvement of other organs. In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) developed diagnostic criteria for juvenile idiopathic inflammatory myopathies and juvenile dermatomyositis. In the absence of muscle biopsies which are infrequently performed in children, scores (in brackets) are assigned to four variables related to muscle weakness, three variables related to skin manifestations, one variable related to other clinical manifestations, and two variables related to laboratory measurements to discriminate idiopathic inflammatory myopathies from non-idiopathic inflammatory myopathies as follows: objective symmetric weakness, usually progressive, of the proximal upper extremities (0.7); objective symmetric weakness, usually progressive, of the proximal lower extremities (0.8); neck flexors relatively weaker than neck extensors (1.9); leg proximal muscles relatively weaker than distal muscles (0.9); heliotrope rash (3.1); Gottron papules (2.1); Gottron sign (3.3); dysphagia or esophageal dysmotility (0.7); the presence of anti-Jo-1 autoantibody (3.9); and elevated serum levels of muscle enzymes (1.3). In the absence of muscle biopsy, a definite diagnosis of idiopathic inflammatory myopathy can be made if the total score is ≥7.5. Patients whose age at onset of symptoms is less than 18 years and who meet the above criteria for idiopathic inflammatory myopathy and have a heliotrope rash, Gottron papules or Gottron sign are deemed to have juvenile dermatomyositis. The mainstay of therapy at the time of diagnosis is a high-dose corticosteroid (oral or intravenous) in combination with methotrexate. Conclusion: For mild to moderate active muscle disease, early aggressive treatment with high-dose oral prednisone alone or in combination with methotrexate is the cornerstone of management. Pulse intravenous methylprednisolone is often preferred to oral prednisone in more severely affected patients, patients who respond poorly to oral prednisone, and those with gastrointestinal vasculopathy. Other steroid-sparing immunosuppressive agents such as cyclosporine and cyclophosphamide are reserved for patients with contraindications or intolerance to methotrexate and for refractory cases, as the use of these agents is associated with more adverse events. Various biological agents have been used in the treatment of juvenile dermatomyositis. Data on their efficacy are limited, and their use in the treatment of juvenile dermatomyositis is considered investigational.

IntroductionPost-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects. We sought to exploit this phenomenon as a potential treatment for PTSD with a clinical trial of patients with PTSD receiving ECT.MethodsTwenty-eight participants with severe depression with comorbid PTSD referred for ECT treatment were randomly assigned to reactivation of a traumatic or non-traumatic memory using script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Assessments were completed by blinded raters. Secondary outcomes included a comparison of the change in heart rate while listening to the script.ResultsTwenty-five patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time.ConclusionsIn this RCT, ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT alone. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression.ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT04027452Identifier: NCT04027452

Background:Nummular eczema may mimic diseases that present with annular configuration and the differential diagnosis is broad.Objective:This article aimed to provide an update on the evaluation, diagnosis, and treatment of nummular eczema.Methods:A PubMed search was performed in using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis” in www.google.com/patents and www.freepatentsonline.com.Results:Nummular eczema is characterized by sharply defined, oval or coin-shaped, erythematous, eczematous plaques. Typically, the size of the lesion varies from 1 to 10cm in diameter. The lesions are usually multiple and symmetrically distributed. Sites of predilection include the lower limbs followed by the upper limbs. The lesions are usually intensely pruritic. The diagnosis is mainly clinical based on the characteristic round to oval erythematous plaques in a patient with diffusely dry skin. Nummular eczema should be distinguished from other annular lesions. Dermoscopy can reveal additional features that can be valuable for correct diagnosis. Biopsy or laboratory tests are generally not necessary. However, a potassium hydroxide wet-mount examination of skin scrapings should be performed if tinea corporis is suspected. Because contact allergy is common with nummular eczema, patch testing should be considered in patients with chronic, recalcitrant nummular eczema. Avoidance of precipitating factors, optimal skin care, and high or ultra-high potency topical corticosteroids are the mainstay of therapy. Recent patents related to the management of nummular eczema are also discussed.Conclusion:With proper treatment, nummular eczema can be cleared over a few weeks, although the course can be chronic and characterized by relapses and remissions. Moisturizing of the skin and avoidance of identifiable exacerbating factors, such as hot water baths and harsh soaps may reduce the frequency of recurrence. Diseases that present with annular lesions may mimic nummular eczema and the differential diagnosis is broad. As such, physicians must be familiar with this condition so that an accurate diagnosis can be made, and appropriate treatment initiated.

Background: Ascaris lumbricoides is the most common helminthic infection. More than 1.2 billion people have ascariasis worldwide. Objective: This article aimed to provide an update on the evaluation, diagnosis, and treatment of ascariasis. Methods: A PubMed search was conducted in February 2020 in Clinical Queries using the key terms “ascariasis” OR “Ascaris lumbricoides”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term “ascariasis” OR “Ascaris lumbricoides” in www.freepatentsonline.com. Results: Ascaris lumbricoides is transmitted through the ingestion of embryonated eggs from fecal- contaminated material. Ascariasis has high endemicity in tropical and subtropical areas. Predisposing factors include poverty, poor sanitation, inadequate sewage disposal, and poor personal hygiene. The prevalence is greatest in children younger than 5 years of age. The majority of patients with intestinal ascariasis are asymptomatic. For those with symptoms, anorexia, nausea, bloating, abdominal discomfort, recurrent abdominal pain, abdominal distension, and intermittent diarrhea are not uncommon. Other clinical manifestations vary widely, depending on the underlying complications. Complications include Löeffler syndrome, intestinal obstruction, biliary colic, recurrent pyogenic cholangitis, cholecystitis, acalculous cholecystitis, obstructive jaundice, cholelithiasis, pancreatitis, and malnutrition. The diagnosis is best established by microscopic examination of fecal smears or following concentration techniques for the characteristic ova. Patients with A. lumbricoides infection warrant anthelminthic treatment, even if they are asymptomatic, to prevent complications from migration of the parasite. Albendazole and mebendazole are the drugs of choice for children and nonpregnant individuals with ascariasis. Pregnant women with ascariasis should be treated with pyrantel pamoate. Recent patents related to the management of ascariasis are also discussed. Conclusion: The average cure rate with anthelminthic treatment is over 95%. Unfortunately, most treated patients in endemic areas become re-infected within months. Health education, personal hygiene, improved sanitary conditions, proper disposal of human excreta, and discontinuing the use of human fecal matter as a fertilizer are effective long-term preventive measures. Targeting deworming treatment and mass anthelminthic treatment should be considered in regions where A. lumbricoides is prevalent.

Background: Hiccups are a universal phenomenon. They are usually benign and selflimited. Persistent or intractable hiccups, although rare, can be debilitating and may indicate the presence of an underlying pathological process. Objective: To familiarize physicians with the pathophysiology, etiology, evaluation, and management of children with hiccups. Methods: A search was conducted on December 10, 2019, in Pubmed Clinical Queries using the key terms "hiccup" OR “hiccough” OR “singultus”. The selected publication types included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies, and reviews (including meta-analysis and narrative reviews) published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Results: Overdistension of the stomach is the most commonly identifiable cause of acute hiccups, followed by gastroesophageal reflux and gastritis. Other causes of hiccups, notably persistent and intractable hiccups, include an underlying gastrointestinal, neurological, cardiovascular, pulmonary, infectious, and psychogenic disorder. Persistent or intractable hiccups can be a harbinger of serious medical pathology. A detailed history and thorough physical examination may provide clues for the etiology of the hiccups. The treatment of hiccups should be directed at the underlying cause whenever possible. Bouts of acute hiccups less than 48 hours rarely require medical intervention as they usually resolve within minutes. Treatment may be considered when hiccups are bothersome, persistent, or intractable. Treatment modalities include lifestyle changes, physical maneuvers, pharmacotherapy and, very rarely, surgical intervention. Conclusion: Acute hiccups are usually benign and self-limiting. Persistent or intractable hiccups can be a harbinger of serious medical pathology. The underlying cause should be treated if possible. There are no formal guidelines for the treatment of hiccups. Currently, most of the methods proposed are based on case reports and anecdotal evidence. Terminating an episode of hiccups can be very challenging for a clinician but may tremendously improve the patient’s quality of life. It is hoped that future well-designed and better-powered studies will provide us with more information on the efficacy of various treatment modalities for hiccups.

Purpose To present the visual and safety outcomes of surgery for primary idiopathic macular holes including predictors of visual acuity and the impact of combined phacovitrectomy surgery. Design Registry-style, prospective, nonrandomized, observational cohort study. Participants Patients with idiopathic macular holes undergoing primary surgery. Methods Surgeons were invited to submit clinical details of all macular hole cases receiving surgery. Baseline demographic and clinical information, and details of surgical intervention were collected. Primary follow-up data were collected at 3 months postoperatively or before revision surgery, and surgeons were also asked to submit data at 12 and 24 months postoperatively. Main Outcome Measures Visual acuity improvement ≥15 letters and ≥0 letters, change in mean visual acuity, visual acuity ≥70 letters (20/40), retinal detachment, and endophthalmitis. Results A total of 2455 eyes of 2366 patients were included in the study, and hole closure was achieved in 95.6% of eyes with a single procedure. Mean baseline vision was 48.3 letters. The proportion of successful eyes improving ≥15 letters at 3, 12, and 24 months was 59.1%, 69.4%, and 68.2%, respectively. The mean improvement in acuity at 3, 12, and 24 months was 16.0, 19.2, and 23.6 letters, and 92.4%, 93.4%, and 95.8% improved ≥0 letters at 3, 12, and 24 months, respectively. Eyes receiving SF6 gas had better visual acuities at all time points postoperatively (adjusted effect 3.4, 3.1, and 4.6 letters better at 3, 12, and 24 months vs. longer-acting gas, respectively). Combined phacovitrectomy in phakic eyes was associated with better corrected visual acuity postoperatively (vs. vitrectomy surgery alone), a difference that vanished when eyes went on to have subsequent cataract surgery. The rate of retinal detachment postoperatively was 1.3%, and the odds of detachment were greater in eyes receiving longer-acting gases versus SF6 gas (adjusted odds ratio, 2.2; 95% confidence interval, 1.04–4.77; P = 0.039). There were no reported cases of endophthalmitis. Conclusions Macular hole surgery substantially improved acuity in approximately two thirds of patients and was seldom associated with loss of vision. SF6 gas was associated with better visual outcomes, an effect that warrants further study.

Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing. Dysfunctional GABA interneuron activity can disrupt the excitatory/inhibitory (E/I) balance in the cortex, which could represent a core pathophysiological mechanism underlying cognitive dysfunction in schizophrenia. Recent research suggests that selective modulation of the GABAergic system is a promising intervention for the treatment of schizophrenia-associated cognitive defects. In this review, we summarized evidence from postmortem and animal studies for abnormal GABAergic neurotransmission in schizophrenia, and how altered GABA interneurons could disrupt neuronal oscillations. Next, we systemically reviewed a variety of up-to-date subtype-selective agonists, antagonists, positive and negative allosteric modulators (including dual allosteric modulators) for α5/α3/α2 GABA(A) and GABA(B) receptors, and summarized their pro-cognitive effects in animal behavioral tests and clinical trials. Finally, we also discuss various representative histone deacetylases (HDAC) inhibitors that target GABA system through epigenetic modulations, GABA prodrug and presynaptic GABA transporter inhibitors. This review provides important information on current potential GABA-associated therapies and future insights for development of more effective treatments.

Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets. Postnatal genetic knock-out of G9a reduces anxiety-related behavior, consistent with the reduction of G9a levels by some medications used to treat anxiety (amitriptyline, imipramine and paroxetine). Conversely, there is increased anxiety-like behavior in mice with GLP haplodeficiency. We sought to determine whether two pharmacological inhibitors of G9a/GLP, UNC0642 and A-366, would have similar effects to genetic G9a/GLP insufficiency. We found that G9a/GLP inhibition with either compound reduced anxiety-like behaviors when administered to adult mice, in conjunction with decreased H3K9 methylation in the brain. In contrast, exposure to these compounds from embryonic day 9.5 (E9.5) until birth increased anxiety-like behaviors and decreased social interaction in adulthood, while H3K9 methylation was at normal levels in the brains of the adult mice. These findings reinforce genetic evidence that G9a/GLP has different effects on anxiety-like behavior at different stages of brain development, and suggest that targeting this histone methyltransferase pathway could be useful for developing new anxiolytic drugs. These data also suggest that antidepressant exposure in utero could have negative effects in adulthood, and further investigation of these effects is warranted.

Background There have been inconsistencies in the histological abnormalities found in the cerebral cortex from patients with schizophrenia, bipolar disorder and major depression. Discrepancies in previously published reports may arise from small sample sizes, inconsistent methodology and biased cell counting. New Method We applied automated quantification of neuron density, neuron size and cortical layer thickness in vast regions of human cortex in psychiatric patients. This method accurately segments DAPI positive cells that are also stained with CUX2 and FEZF2. Cortical layer thickness, neuron density and neuron size were automatically computed for each cortical layer in numerous Brodmann areas. Results We did not find pronounced cytoarchitectural abnormalities in the anterior cingulate cortex or orbitofrontal cortex in patients with schizophrenia, bipolar disorder or major depressive disorder. Comparison with existing methods. There were no significant differences in layer thickness measured in immunohistochemically stained slides compared with traditional Nissl stained slides. Automated cell counts were correlated, reliable and consistent with manual counts, while being much less time-consuming. Conclusion We demonstrate the validity of using a novel automated analysis approach to post-mortem brain tissue. We were able to analyze large cortical areas and quantify specific cell populations using immunohistochemical markers. Future analyses could benefit from efficient automated analysis.

OBJECTIVE The main aim of the current study was to investigate epigenetic alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk factors for suicidal behavior. We also aimed to analyze the epigenetic alterations in two different tissues as epigenetic mechanisms are tissue specific. These epigenetic changes may lead to a better prediction of suicidal behavior. METHODS Direct CpG methylation analysis was carried out on genomic DNA from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and from post-mortem brain tissues of nine suicide victims and 11 controls. We used bisulfite pyrosequencing to assess the contributions of six CpG sites including the rs6313 (C102T) site in the first exon of HTR2A in suicide attempters and suicide victims. RESULTS DNA methylation analysis did not find a significant difference in CpG methylation between suicide attempters and non-attempters (P=0.759) or between suicide victims and controls (P=0.189). We found a strong positive correlation between CpG methylation levels in blood and saliva (r=0.547, P

Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manifests differently in males and females, including abnormalities in the dopamine system that are also seen in Fmr1-knockout (KO) mice. We investigated sex differences in dopamine signaling in Fmr1-KO mice in response to L-stepholidine, a dopamine D1 receptor agonist and D2 receptor antagonist. We found significant sex differences in basal levels of phosphorylated protein kinase A (p-PKA) and glycogen synthase kinase (GSK)-3β in wild type mice that were absent in Fmr1-KO mice. In wild-type mice, L-stepholidine increased p-PKA in males but not female mice, decreased p-GSK-3 in female mice and increased p-GSK-3 in male mice. Conversely, in Fmr1-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males.

Importance Visual outcomes following diabetic vitrectomy have not previously been studied in an Australian population. Background This analysis aimed to (1) determine the rate of, and factors associated with visual success following diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and (2) investigate factors predisposing to early progression to diabetic retinopathy (DR) requiring vitrectomy. Design Retrospective, population-based audit. Participants All patients undergoing vitrectomy for the complications of DR in South Australia (SA) and the Northern Territory (NT) between 2007 and 2011. Methods Medical records were audited and data collected, including demographics, diabetic history, past treatment for DR, indication for vitrectomy, and visual acuity pre- and post-operatively. Outcome measures Visual success (gain of ≥ 15 ETDRS letters) at 6 and 12 months post-operatively. Results 495 diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable or improved vision at 1 year post-operatively. There was no significant difference between Indigenous and non-Indigenous eyes achieving visual success (P=0.929). Timely pre-operative laser treatment (P=0.03) and pre-operative visual acuity (P=0.01) were the predominant factors associated with visual success. Conclusions Indigenous patients are just as likely to have improved vision following diabetic vitrectomy as non-indigenous Australians. However, the small subset of Indigenous patients with blind eyes prior to vitrectomy are significantly less likely to improve from surgery. The underlying factors associated with poor outcomes in this group requires further exploration.

The Uniaxial Compressive Strength (UCS) of rock cores is a key parameter for design analysis of rock engineering projects such as rock tunnels and piles in rockets. Diametral and axial point load tests on cylinder cores have been used to obtain Point Load Strength Index (PLSI). This PLSI is correlated to UCS. Recently, point load tests on irregular lumps are also used to obtain PLSI which is then correlated to UCS. However, the data on this correlation are very limited, especially for Hong Kong rocks. This paper presents the methodology for specimen preparation, testing, and data analysis. Results from irregular lump point load tests, diametral and axial point load tests, and uniaxial compressive tests (a total of 754 specimens of granitic rocks were tested) are then presented, analyzed, and discussed. A correlation between PLSI from irregular lump tests and UCS is established with a suitable size correction function. It is found that the I s(50) of the slightly decomposed Granite is between 7.31 MPa and 8.5 MPa. The I s(50) of the altered rock is 2.35 MPa, where the rock containing weakness plane is 5.59 MPa. The moderately decomposed Granite varies from 2.28 MPa to 4.92 MPa. The weathering affected the PLIS a lot. It is found that the values of power index value m in the size correction function is 0.443–0.600 for slightly decomposed granite (fine to coarse grains) and 0.545–5.562 for moderately decomposed granite (fine to medium and medium grains). Based on our study, for slightly decomposed coarse grain and fine to medium grain Granite, the size correction factor F = ( D e /50) 0.44 (lower bound) is recommend; while for all other weathering conditions and grain sizes, the size correction factor F = ( D e /50) 0.55 (lower bound) is recommended. The correlation between the UCS and PLSI Is (50) of irregular lumps is found to be 22.27, which is very close to the values of 21.61 and 21.72 for diametral and axial PL tests using the size correction factor of F = ( De /50) 0.45 . This indicates that the correlation between UCS and PLSI from point load tests on irregular lumps established in this paper is reliable.

Objective Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. Methods NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. Results ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. Conclusions ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer.

The possibility of testing irregular lumps under the point load strength test (PLST) was investigated theoretically and experimentally. In particular, a new analytical solution for stress d...

Posttraumatic stress disorder (PTSD) can develop after exposure to severe psychological trauma, leaving patients with disabling anxiety, nightmares, and flashbacks. Current treatments are only partially effective, and development of better treatments is hampered by limited knowledge of molecular mechanisms underlying PTSD. We have discovered that the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP51) form a protein complex that is elevated in PTSD patients compared with unaffected control subjects, subjects exposed to trauma without PTSD, and patients with major depressive disorder (MDD). The GR-FKBP51 complex is also elevated in fear-conditioned mice, an aversive learning paradigm that models some aspects of PTSD. Both PTSD patients and fear-conditioned mice had decreased GR phosphorylation, decreased nuclear GR, and lower expression of 14-3-3e, a gene regulated by GR. We created a peptide that disrupts GR-FKBP51 binding and reverses behavioral and molecular changes induced by fear conditioning. This peptide reduces freezing time and increases GR phosphorylation, GR-FKBP52 binding, GR nuclear translocation, and 14-3-3e expression in fear-conditioned mice. These experiments demonstrate a molecular mechanism contributing to PTSD and suggest that the GR-FKBP51 complex may be a diagnostic biomarker and a potential therapeutic target for preventing or treating PTSD.