A comparative study of histopathologic features in alopecia areata and pattern hair loss.

BACKGROUND: When peribulbar infiltrates are absent, other histopathologic findings are necessary to distinguish alopecia areata (AA) from pattern hair loss (PHL). The purpose of this study is to determine which histopathologic features are most useful for differentiation. METHODS: A retrospective slide review was conducted of AA and PHL scalp biopsy specimens from 2014 to 2019 at a tertiary referral center. RESULTS: Ninety-six cases were retrieved, of which 38 were AA. Peribulbar infiltrates were identified in 24 AA (63.2%) cases. A catagen/telogen shift was observed more frequently in AA than PHL (25 cases, 65.5% vs. 10 cases, 17.2%; p ≤ 0.0001). Lymphocytes (4 cases, 10.5% vs. 1 case, 1.7%; p = 0.058) and melanin (25 cases, 65.8% vs. 5 cases, 8.6%; p ≤ 0.0001) in fibrous tracts were more common in AA. Apoptotic bodies within vellus hairs were more frequently identified in AA (32 cases, 84.2% vs. 37 cases, 63.8%; p = 0.030). Small dystrophic follicles were also more common in AA (16 cases, 42.1% vs. 1 case, 1.7%; p < 0.0001). CONCLUSIONS: Common features of AA other than peribulbar infiltrates include a catagen/telogen shift, melanin in fibrous tracts, and small dystrophic follicles. Practitioners should consider these features when distinguishing AA from PHL in specimens without peribulbar infiltrates. The retrospective design limits our ability to exclude multifactorial alopecia, such as telogen effluvium.

Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.

There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

Liver disease and outcomes among COVID-19 hospitalized patients - A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has been a challenge globally. In severe acute respiratory syndrome (SARS) epidemic 60% of patients had hepatic injury, due to phylogenetic similarities of the viruses it is assumed that COVID-19 is associated with acute liver injury. In this meta-analysis, we aim to study the occurrence and association of liver injury, comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations with outcomes. MATERIALS AND METHODS: Data from observational studies describing comorbid chronic liver disease, acute liver injury, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and outcomes of COVID-19 hospitalized patients from December 1, 2019, to June 30, 2020 was extracted following PRISMA guidelines. Adverse outcomes were defined as admission to intensive care unit (ICU), oxygen saturation <90%, invasive mechanical ventilation (IMV), severe disease and in-hospital mortality. Odds ratio (OR) and 95% confidence interval (95% CI) were obtained. RESULTS: 24 studies with 12,882 confirmed COVID-19 patients were included. Overall prevalence of CM-CLD was 2.6%, COVID-19-ALI was 26.5%, elevated AST was 41.1% and elevated ALT was 29.1%. CM-CLD had no significant association with poor outcomes (pooled OR: 0.96; 95% CI: 0.71-1.29; p=0.78). COVID-19-ALI (1.68;1.04-2.70; p=0.03), elevated AST (2.98; 2.35-3.77; p<0.00001) and elevated ALT (1.85;1.49-2.29; p<0.00001) were significantly associated with higher odds of poor outcomes. CONCLUSION: Our meta-analysis suggests that acute liver injury and elevated liver enzymes were significantly associated with COVID-19 severity. Future studies should evaluate changing levels of biomarkers amongst liver disease patients to predict poor outcomes of COVID-19 and causes of liver injury during COVID-19 infection.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.

Drosophila homologues of adenomatous polyposis coli (APC) and the formin diaphanous collaborate by a conserved mechanism to stimulate actin filament assembly.

BACKGROUND: Vertebrate APC collaborates with Dia through its Basic domain to assemble actin filaments. RESULTS: Despite limited sequence homology between the vertebrate and Drosophila APC Basic domains, Drosophila APC1 collaborates with Dia to stimulate actin assembly in vitro. CONCLUSION: The mechanism of actin assembly is highly conserved over evolution. SIGNIFICANCE: APC-Dia collaborations may be crucial in a wide range of animal cells. Adenomatous polyposis coli (APC) is a large multidomain protein that regulates the cytoskeleton. Recently, it was shown that vertebrate APC through its Basic domain directly collaborates with the formin mDia1 to stimulate actin filament assembly in the presence of nucleation barriers. However, it has been unclear whether these activities extend to homologues of APC and Dia in other organisms. Drosophila APC and Dia are each required to promote actin furrow formation in the syncytial embryo, suggesting a potential collaboration in actin assembly, but low sequence homology between the Basic domains of Drosophila and vertebrate APC has left their functional and mechanistic parallels uncertain. To address this question, we purified Drosophila APC1 and Dia and determined their individual and combined effects on actin assembly using both bulk fluorescence assays and total internal reflection fluorescence microscopy. Our data show that APC1, similar to its vertebrate homologue, bound to actin monomers and nucleated and bundled filaments. Further, Drosophila Dia nucleated actin assembly and protected growing filament barbed ends from capping protein. Drosophila APC1 and Dia directly interacted and collaborated to promote actin assembly in the combined presence of profilin and capping protein. Thus, despite limited sequence homology, Drosophila and vertebrate APCs exhibit highly related activities and mechanisms and directly collaborate with formins. These results suggest that APC-Dia interactions in actin assembly are conserved and may underlie important in vivo functions in a broad range of animal phyla.

Correlates of diabetes mellitus and hypertension in India: Change as evidenced from NFHS- 4 and 5 during 2015-2021.

Both diabetes mellitus (DM) and hypertension (HTN) have been on the rise in recent decades all over the world more remarkably in developing countries like India. We intend to measure the prevalence of DM and HTN in the Indian population and to compare the trends and various correlates of these diseases in NFHS (National Family Health Survey)-4 and 5. Data of NFHS-4 and 5 were accessed from dhs program website. All statistical analyses were done in SAS (version 9.4). Mixed effects survey logistic regression models were used for estimating odds ratio (OR).p-values <0.05 were considered significant .1,637,762 individual case entries were evaluated. Both the diseases showed an increasing trend as per the advancing age in both sexes. The highest prevalence of DM is seen in the age group of 45-49 years (7.8%) in females and > 50 years (11.9%) in males as per NFHS-5. Similarly, the highest prevalence of HTN was seen in the age group of45-49 years (31.2%) in females and > 50 years (41.4%) in males as per NFHS-5. The OR (95% CI) of prevalence of DM, HTN and both the diseases in age group >50 years was 14.46 (13.14-15.7), 16.65 (15.78-17.6), 79.5 (64.76-97.73) respectively when compared to reference age group15-19 years. Highest odds for having both DM, HTN concurrently was in age >50 years with aOR(95% CI) 65.32 (52.26-72.63) in NFHS 4 and 35.57 (97.47-45.53) in NFHS 5.Rise in prevalence of DM, HTN and concurrent presence is noted with an apparent increase in cases.

Outcomes of COVID-19 amongst patients with ongoing use of inhaled corticosteroids - a systematic review & meta-analysis.

Background: WHO quoted the numbers for the Coronavirus disease 2019 (COVID-19) pandemic as of August 2021 were 200 million cases with over 4 million deaths globally. COVID-19 is associated with several respiratory pathologies. Inhaled corticosteroids (ICS) are used to improve lung function by reducing inflammation, edema, mucus secretion, and inhibiting various cytokine activities. However, there is limited data on the effect of ICS usage in patients with COVID-19. In this study, we aim to evaluate the association between the use of ICS and the outcomes in COVID-19 patients compared to standard COVID-19 treatment. Methods: We followed PRISMA guidelines and MOOSE protocol for conducting the systematic review and meta-analysis comparing ICS and standard COVID-19 therapy. A search on PubMed is conducted yielding 270 articles of which 6 manuscripts are finalized for inclusion in the study. Patients with COVID-19 are identified from the studies based on confirmed positive RT-PCR tests. Hospitalization, ICU admission, and mortality are selected as the outcomes of our study. Using RevMan 5.3, we performed random-effects models to estimate the pooled effect size (pooled odds ratio), 95% confidence interval (95% CI), and heterogeneity (I2). Forest plots are obtained and p <0.05 is considered statistically significant. Results: Our study involves the comparison of ICS vs Non-ICS for mortality (N= 207,842 vs 166,217), ICU hospitalization (N= 1,084 vs 9,425), and the risk of hospitalization (N= 1,273 vs 1,676).Of the six studies, five reported mortality. We found a higher mortality rate in patients with asthma (60.88%, 107/160) and chronic obstructive pulmonary disease (COPD) (68.46%, 382/558) among ICS users. The overall mortality is 7.49% (107/1428). We found that ICS use was associated with higher odds of mortality (OR=1.45 95%CI: 1.10-1.91; p=0.009, I2= 68%) amongst COVID-19 patients. In subgroup analysis, higher odds of mortality among COPD patients using ICS was noted [pooled OR: 1.52 (1.24-1.86); p<0.0001; I2=0%]. However, no significant association between ICS and mortality was observed among asthma patients. Conclusion: ICS is associated with increased mortality and risk for hospitalization in patients with COVID-19 as compared to standard non-steroid-based COVID-19 therapy. It is crucial for healthcare providers to carefully evaluate the potential risks and benefits of ICS usage in the context of COVID-19 management to optimize patient outcomes and safety.

An Overview of Psychological Analysis of Breast Cancer Patients undergoing Modified Radical Mastectomy and Breast Conservation Surgery and its impact on Objectified Body Consciousness at a Tertiary Care Cancer Centre in South India.

BACKGROUND: Breast cancer is the most common cancer among females, and surgery plays a central role in its treatment. Surgical treatments may have a negative psychological impact on women's mental health regarding their body image. The purpose of this study was to compare the psychological health insights pertaining to objectified body consciousness scores before and after the surgery and also to observe whether these scores were comparable across the surgery types. MATERIALS AND METHODS: This retrospective analysis of prospectively maintained data included 706 breast carcinoma patients who underwent either Breast Conservation Surgery or Modified Radical Mastectomy at tertiary care Cancer Centre, between the years 2020 to 2021. A validated questionnaire of Objectified Body Consciousness was used to obtain responses at diagnosis and at 6 months postsurgery and final scores were calculated for both instances. Two sample t-tests/analysis of variance and Chi-square tests were used to compare continuous and categorical variables respectively. RESULTS: Out of total 706 breast cancer patients, 402 patients underwent Breast Conservation Surgery and 304 underwent Modified radical mastectomy procedure. A statistically significant change was seen in the mean Objectified Body Consciousness Score (14.22 ± 15.44) for all patients when compared preoperatively(72.72 ± 11.38) and postoperatively(60.15 ± 17.58). This change was higher in the Modified Radical Mastectomy group(29.38 ± 11.53). Also, statistically significant rise in scores was seen with increasing age. CONCLUSION: We could affirmatively conclude in our study that younger breast cancer patients and all patients who underwent a Modified Radical Mastectomy, had more psychological apprehension with the body image postsurgery, signifying these groups should be encouraged by healthcare professionals to reach out for counselling at the earliest.

Prevalence of active and passive smoking among asthma and asthma-associated emergency admissions: a nationwide prevalence survey study.

Asthma affects 7% of children and 8% of adults in the United States. There is a paucity of studies examining the association between passive smoking and an increased risk of asthma exacerbations that led the authors to examine the association between various modes of smoking and rates of asthma exacerbations. A retrospective cross-sectional/case-control study was conducted using the National Health and Nutrition Examination Survey dataset (2013-2018). Out of 312,979 respondents, 35,758 (11.43%) had a history of asthma, 9083 (2.9%) had asthma attacks in the past year, and 4731 (1.51%) had asthma-related emergency room admissions in the past year. Prevalence of asthma-related emergency admissions were higher among active cigarette smoking (46.25 vs 35.46%), e-cigarette smoking (26.63 vs 16.07%), and passive smoking at home (37.53 vs 25.67%), workplace passive smoking (14.35 vs 12.11%), in bar (32.38 vs 26.16%), and car (26.21 vs 14.44%) (p < 0.0001). In multivariate regression analysis, we found regular cigarette smoking (OR 1.13, 95% confidence interval (CI) 1.009-1.260, p = 0.0252), e-cigarette (OR 2.13, 95% CI 1.92-2.36, p = 0.0043), cigar use (OR 1.21, 95% CI 1.1-1.33, p < 0.001), ultra-long cigarette length (OR 4.85, 95% CI 3.33-7.06, p < 0.0001), and passive smoking (OR 5.25, 95% CI 3.43-8.06, p < 0.0001) were associated with increased rates of asthma exacerbations over last 12 months. The study shows increased odds of asthma exacerbations among those using ultra-long cigarettes, e-cigarettes, and cigars. Consequently, passive inhalation from even a single smoker in the home, workplace, bars and cars is associated with worsening outcomes in asthma patients.

Cardiac Sarcoidosis Diagnostic Challenges and Management: A Case Report and Literature Review.

Sarcoidosis can be presented as cardiac sarcoidosis (CS), which is challenging to diagnose due to its clinical silence. Ventricular arrhythmias and atrioventricular blocks can be fatal and cause sudden death in patients with cardiac sarcoidosis. Five percent of sarcoidosis patients have clinically evident cardiac sarcoidosis. However, autopsy reports and imaging studies have shown a higher prevalence of cardiac involvement. Early recognition is important to prevent such detrimental consequences. Cardiac sarcoidosis is increasingly being diagnosed owing to increased awareness among physicians and new diagnostic tools like MRI and positron emission tomography (PET) scan replacing traditional endomyocardial biopsy. A definitive diagnosis of CS remains challenging due to the non-specific clinical findings that can present similar symptoms of common cardiac disease; therefore, the imaging and biopsies are substantial for diagnosis confirmation. Pharmacological and Implantable devices are two main therapeutic approaches in cardiac sarcoidosis, in which steroids and pacemaker therapy have shown better outcomes. This review summarizes the available data related to the prevalence, prognosis, diagnosis, and management of cardiac sarcoidosis.

Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study.

Background: There is an increased trend of e-cigarette but the toxic effects of e-cigarette metabolites are not widely studied especially in liver disease. Hence, we aimed to evaluate the prevalence and patterns of recent e-cigarette use in a nationally representative sample of US adults and adolescents and its association amongst respondents with liver disease. Methods: We conducted a retrospective cross-sectional study using National Health and Nutrition Examination Survey (NHANES) database from 2015 to 2018. The self-reported NHANES questionnaire was used to assess liver disease (MCQ160L, MCQ170L and MCQ 510 (a-e)), e-cigarette use (SMQ900) and traditional smoking status (SMQ020 or SMQ040). We conducted univariate analysis and multivariable logistic regression models to predict the association of e-cigarette use, traditional smoking and dual smoking amongst the population with liver disease. Results: Out of total 178,300 respondents, 7,756 (4.35%) were e-cigarette users, 48,625 (27.27%) traditional smoking, 23,444 (13.15%) dual smoking and 98,475 (55.23%) non-smokers. Females had a higher frequency of e-cigarette use (49.3%) compared to dual (43%) and traditional smoking (40.8%) (P < 0.0001). Respondents with a past history of any liver disease have lower frequency of e-cigarette use compared to dual and traditional smoking, respectively (2.4% vs. 6.4% vs. 7.2%; P < 0.0001). In multivariate logistic regression models, we found that e-cigarette users (odds ratio (OR): 1.06; 95% confidence interval (CI): 1.05 - 1.06; P < 0.0001) and dual smoking (OR: 1.50; 95% CI: 1.50 - 1.51; P < 0.0001) were associated with higher odds of having history of liver disease compared to non-smokers. Conclusion: Our study found that despite the low frequency of e-cigarette use in respondents with liver disease, there was higher odds of e-cigarette use amongst patients with liver disease. This warrants the need for more future prospective studies to evaluate the long-term effects and precise mechanisms of e-cigarette toxicants on the liver.

Mucormycosis of the Breast in a Patient With Breast Carcinoma After COVID-19 Pneumonia.

Mucormycosis is a rare, but potentially fatal, fungal infection which is caused by mucormyctes. These forms of fungi are typically known to infect immuno-compromised individuals but are rare in immunocompetent individuals. Herein, we report the case of a 52 year-old female who was diagnosed with right breast carcinoma in Manipal Hospital, a tertiary cancer care center. The patient was a known diabetic and hypertensive and who had recently recovered from coronavirus disease-2019 (COVID-19) pneumonia. In the due course of management, she developed mucormycosis infection at the operative site in her right breast where she had a radiation therapy-induced wound. This patient was successfully treated with an aggressive regimen of early surgical debridement along with administration of systemic amphotericin B.

An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.

Objective: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer. Materials and Methods: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category. Results: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively. Conclusion: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.

E93R substitution of Escherichia coli FtsZ induces bundling of protofilaments, reduces GTPase activity, and impairs bacterial cytokinesis.

Recently, we found that divalent calcium has no detectable effect on the assembly of Mycobacterium tuberculosis FtsZ (MtbFtsZ), whereas it strongly promoted the assembly of Escherichia coli FtsZ (EcFtsZ). While looking for potential calcium binding residues in EcFtsZ, we found a mutation (E93R) that strongly promoted the assembly of EcFtsZ. The mutation increased the stability and bundling of the FtsZ protofilaments and produced a dominating effect on the assembly of the wild type FtsZ (WT-FtsZ). Although E93R-FtsZ was found to bind to GTP similarly to the WT-FtsZ, it displayed lower GTPase activity than the WT-FtsZ. E93R-FtsZ complemented for its wild type counterpart as observed by a complementation test using JKD7-1/pKD3 cells. However, the bacterial cells became elongated upon overexpression of the mutant allele. We modeled the structure of E93R-FtsZ using the structures of MtbFtsZ/Methanococcus jannaschi FtsZ (MjFtsZ) dimers as templates. The MtbFtsZ-based structure suggests that the Arg(93)-Glu(138) salt bridge provides the additional stability, whereas the effect of mutation appears to be indirect (allosteric) if the EcFtsZ dimer is similar to that of MjFtsZ. The data presented in this study suggest that an increase in the stability of the FtsZ protofilaments is detrimental for the bacterial cytokinesis.

Asymptomatic Left Atrial Myxoma Treated With Minimally Invasive Surgical Approach.

Myxomas, being the most common primary benign tumor among all cardiac tumors, occur rarely with a very low incidence rate. Myxomas can cause various clinical manifestations or can be diagnosed incidentally. Some patients with cardiac myxomas are completely asymptomatic. Cardiac myxomas cause life-threatening complications, thus early diagnosis is imperative. We are reporting a case of atrial myxoma in a 38-year-old female without any significant past medical history, who came to our clinic for cardiology evaluation prior to plastic surgery. The elliptical mobile mass, located in the left atrium with its attachment to the interatrial septum, was diagnosed by transthoracic echocardiography. The patient was referred for surgery and a minimally invasive surgical approach was chosen. A histological report confirmed the diagnosis of myxoma. The patient recovered well. Three years of follow-up did not reveal any signs of recurrence of the tumor. We are also analyzing 20 previously published cases of asymptomatic myxomas and myxomas treated with a minimally invasive surgical approach, reported in the PubMed database for the last 20 years (2001-2021) in the adult patient population (age 19 and over). The aim of this study is to highlight the asymptomatic presentation of cardiac myxomas and to underline the advantages of a minimally invasive surgical approach. In summary, asymptomatic cardiac myxomas are rare incidental findings. Attention to subtle symptoms during a physical exam and scrupulous history-taking can provide a clue to this diagnosis. Early diagnosis of cardiac myxomas is crucial to prevent life-threatening complications. Minimally invasive surgery is a promising alternative approach to standard open-heart surgery for treating cardiac myxomas, providing faster recovery and higher patient satisfaction with surgical care.

EB1 Directly Regulates APC-Mediated Actin Nucleation.

EB1 was discovered 25 years ago as a binding partner of the tumor suppressor adenomatous polyposis coli (APC) [1]; however, the significance of EB1-APC interactions has remained poorly understood. EB1 functions at the center of a network of microtubule end-tracking proteins (+TIPs) [2-5], and APC binding to EB1 promotes EB1 association with microtubule ends and microtubule stabilization [6, 7]. Whether EB1 interactions govern functions of APC beyond microtubule regulation has not been explored. The C-terminal basic domain of APC (APC-B) directly nucleates actin assembly, and this activity is required in vivo for directed cell migration and for maintaining normal levels of F-actin [8-10]. Here, we show that EB1 binds APC-B and inhibits its actin nucleation function by blocking actin monomer recruitment. Consistent with these biochemical observations, knocking down EB1 increases F-actin levels in cells, and this can be rescued by disrupting APC-mediated actin nucleation. Conversely, overexpressing EB1 decreases F-actin levels and impairs directed cell migration without altering microtubule organization and independent of its direct binding interactions with microtubules. Overall, our results define a new function for EB1 in negatively regulating APC-mediated actin assembly. Combining these findings with other recent studies showing that APC interactions regulate EB1-dependent effects on microtubule dynamics [7], we propose that EB1-APC interactions govern bidirectional cytoskeletal crosstalk by coordinating microtubule and actin dynamics.

Megacell phenotype and its relation to metabolic alterations in transketolase deficient strain of Bacillus pumilus.

Fermentation with transketolase (tkt) deficient strain of Bacillus is the only reported industrially viable process for production of D-ribose, a commercially important pentose sugar. In addition to direct effects of tkt deficiency, the mutation in non-oxidative part of pentose phosphate pathway (PPP) is known to display several unexpected physiological characteristics such as decreased ability to utilize D-glucose, altered carbon catabolite repression, lack of motility, etc. Here we demonstrate the morphological plasticity of tkt deficient strain of Bacillus pumilus ATCC 21951 and its possible relation with D-ribose productivity, a measure of carbon flux through PPP. The bacilli divide normally in nutrient rich media such as Luria-Bertani (LB) broth while showing cell elongation of up to 20-fold without a visible septum accompanied by moderate to high extracellular D-ribose accumulation in glucose-rich media. The cells stained with DAPI (4'-6-diamidino-2-phenylindole) and anti FtsZ antibody showed nucleoid separation and Z-ring formation in LB broth but not in glucose-rich media. FtsZ protein is known to localize at the future division site forming a ring, called Z-ring, at an early stage in cytokinesis. The strain experiences inhibition or delay in Z-ring formation resulting in cell elongation, possibly due to its altered cell membrane composition resulting from tkt deficiency. We hypothesize that the lack of PPP intermediates may have two effects on the strain: (i) altered the cell membrane leading to delay in Z-ring formation and cell elongation; and (ii) induction of genes of the oxidative part of PPP resulting in D-ribose accumulation. Nutrient rich media such as LB broth may alleviate these metabolite deficiencies thereby restoring normal cell division and inhibiting excessive D-ribose accumulation. The D-ribose productivity and cell elongation may therefore be co-morbid. The results have implications in designing optimal media and monitoring strategy based on morphological analysis.

Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover.

Cell motility depends on tight coordination between the microtubule (MT) and actin cytoskeletons, but the mechanisms underlying this MT-actin cross talk have remained poorly understood. Here, we show that the tumor suppressor protein adenomatous polyposis coli (APC), which is a known MT-associated protein, directly nucleates actin assembly to promote directed cell migration. By changing only two residues in APC, we generated a separation-of-function mutant, APC (m4), that abolishes actin nucleation activity without affecting MT interactions. Expression of full-length APC carrying the m4 mutation (APC (m4)) rescued cellular defects in MT organization, MT dynamics, and mitochondrial distribution caused by depletion of endogenous APC but failed to restore cell migration. Wild-type APC and APC (m4) localized to focal adhesions (FAs), and APC (m4) was defective in promoting actin assembly at FAs to facilitate MT-induced FA turnover. These results provide the first direct evidence for APC-mediated actin assembly in vivo and establish a role for APC in coordinating MTs and actin at FAs to direct cell migration.