Maternal Periodontitis Prevalence and its Relationship with Preterm and Low-Birth Weight Infants: A Hospital-Based Research.

Introduction: Overall wellness depends on oral health. Epidemiological, clinical, and laboratory studies have linked periodontitis to some systemic diseases. Pregnancy labor, contractions, and delivery are controlled by prostaglandin (PGE 2) levels rise during pregnancy, and labor begins when a critical threshold is reached. These associations support the underlying cause of maternal periodontal disease. Materials and Methods: In the study, 3,885 pregnant women aged 18-40 had singleton babies. All mother participants were clinically evaluated by the primary investigator. The periodontal disease is defined using a few parameters. Based on that the prevalence rate will be evaluated. Result: The prevalence of preterm babies' mothers affected with periodontitis was 0.5% and low-birth weight babies' mothers affected with periodontitis was 1.6%. So, there was a significant result is there. Conclusion: Periodontal health and preterm LBW newborns are highly associated with periodontitis in research. It may modify preterm birth and LBW risk factors. Thus, dentists detect and treat this sickness early, preventing pregnancy difficulties in sensitive mothers.

Indole-based aryl sulfides target the cell wall of Staphylococcus aureus without detectable resistance.

Sulfur-containing classes of the scaffold "Arylthioindoles" have been evaluated for antibacterial activity; they demonstrated excellent potency against methicillin-resistant Staphylococcus aureus (MRSA) as well as against vancomycin-resistant strains and a panel of clinical isolates of resistant strains. In this study, we have elucidated the mechanism of action of lead compounds, wherein they target the cell wall of S. aureus. Further, S. aureus failed to develop resistance against two lead compounds tested in a serial passage experiment in the presence of the compounds over a period of 40 days. Both the compounds demonstrated comparable in vivo efficacy with vancomycin in a neutropenic mice thigh infection model. The results of these antibacterial activities emphasize the excellent potential of thioethers for developing novel antibiotics and may fill in as a target for the adjustment of accessible molecules to develop new powerful antibacterial agents with fewer side effects.

Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a preclinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth.

Photoisomerization of phytochrome chromophore models: an XMS-CASPT2 study.

Phytochromes are a superfamily of photoreceptors that harbor linear tetrapyrroles as chromophores. Upon light illumination, the linear tetrapyrrole chromophore undergoes a double bond isomerization which starts a photocycle. In this work, we studied the photoisomerization of chromophore models designed based on the C- and D-rings of the phycocyanobilin (PCB) chromophore. In total, five different models with varying substitutions were investigated. Firstly, the vertical excitation energies were benchmarked using different computational methods to establish the relative order of the excited states. Based on these calculations, we computed the photoisomerization profiles using the extended multi-state (XMS) version of the CASPT2 method. The profiles were obtained for both the clockwise and counterclockwise rotations of the C15C16 bond in the Z and E isomers using a linear interpolation of internal coordinates between the Franck-Condon and MECI geometries. In the minimal chromophore model that lacks the substitutions at the pyrrole rings, the isomerization involves both C14-C15 and C15C16 bonds of the methine bridge between the C- and D-rings, resembling the hula-twist motion. The MECIs are characterized by a partial charge transfer between the two pyrrole rings pointing towards a twisted intramolecular charge transfer. Systematic introduction of substituents leads to an increase in the steric repulsion between the two pyrrole rings causing a pretwist of the dihedral around the C15C16 bond, which creates a preference for the counterclockwise isomerization. An introduction of the carbonyl group at the D-ring increases the extent of charge transfer which changes the isomerization mechanism from hula-twist to one-bond flip.

Whole exome sequencing and transcript analysis discover a novel pathogenic splice site mutation in DCAF17 gene underlying Woodhouse-Sakati syndrome.

Woodhouse-Sakati syndrome (WSS) is an extremely rare multisystemic disorder with neuroendocrine dysfunctions. It is characterized by hypogonadism, alopecia, diabetes mellitus, intellectual disability and progressive extrapyramidal syndrome along with radiological features of small pituitary gland, progressive frontoparietal white matter changes and abnormal accumulation of iron on globus pallidus. WSS is caused by mutations in DCAF17 gene that encodes for DDB1 and CUL4 associated factor 17. In this study, we report a 17-year-old boy with clinical and radiological features of WSS including mild global developmental delay, mild intellectual disability, sensorineural hearing loss, progressive extrapyramidal syndrome, alopecia, hypogonadotropic hypogonadism and dysmorphic features. Whole exome sequencing analysis revealed a novel potentially pathogenic splice donor site variant (c.458+1G>T) on the intron 4 of DCAF17 gene. Transcript analysis revealed splicing ablation resulting in aberrant splicing of exons 3 and 5 and skipping of exon 4 (c.322_458del). This results in a frameshift and is predicted to cause premature termination of protein synthesis resulting in a protein product of length 120 amino acids (p.[Gly108Ilefs*14]). Our study identified a novel pathogenic variant causing WSS in a patient and expands the spectrum of clinical and genetic characteristics of patients with WSS.

Association of Body Mass Index with Angiographic Severity of Coronary Artery disease in patients with Acute Coronary Syndrome.

Coronary artery disease (CAD) is the leading cause of death in developed and developing countries. Associated co-morbidities like diabetes, hypertension and obesity are making the situation worse. WHO enlisted obesity as an epidemic which also affects a great number of young population. Some recent studies showed the presence of an apparent paradoxical relationship between obesity and cardiovascular prognosis in certain subsets of patents. As BMI is an established marker of obesity; an attempt has been made to assess relationship between BMI and angiographic severity of coronary artery disease in Acute Coronary Syndrome (ACS) patients of Bangladeshi origin. To assess the association between body mass index and angiographic severity of coronary artery disease in patients with acute coronary syndrome; this cross sectional analytical study was conducted in the Department of Cardiology, Mymensingh Medical College Hospital (MMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU) from December 2016 to February 2018 among purposively selected 65 patients. Relevant ethical issues were taken into consideration. Coronary angiogram was done in the same index hospitalization period. After coronary angiogram performed patients were grouped into two groups according to their BMI. Patients with BMI <25kg/m² as Group I and those ≥25kg/m² as Group II. Angiographic severity of coronary artery disease was assessed by vessel score and Syntax score. Mean age of Group I was 54.45±10.42 years, while in Group II it was 50.76±8.89 years reflecting the early presentation of higher BMI patients. Male to female ratio was 12:1. Mean BMI of Group I and Group II was 22.56±1.59 and 28.67±2.64 respectively. In Group I, 10(25.0%) had single vessel lesion, 15(37.5%) had double vessel lesion and 14(35.0%) had triple vessel lesion, while in Group II, 6(24.0%) had single vessel lesion, 12(48.0%) had double vessel lesion and 5(20.0%) had triple vessel lesion. Mean Syntax score of Group I and Group II was 13.18±8.45 and 10.42±7.14 respectively. Patients in the increasing BMI class had a higher prevalence of diabetes, hypertension and dyslipidaemia. A negative correlation was observed between BMI and angiographic severity (Vessel score, Syntax score and HRCA e.g. LM disease) of CAD indicating that patients with higher BMI had a lower coronary artery disease (CAD) severity than their normal BMI counterparts. Patients with high BMI have a lower CAD severity than usually expected. After adjustment for co-morbidities, BMI was not found as an independent predictor of severity of coronary artery disease.

Bickerstaff brainstem encephalitis: clinical, neurophysiological, laboratory and postmortem findings of a case presenting as encephalomyelitis.

Our patient was admitted to hospital with a 1-week history of an upper respiratory tract infection and a rapidly progressive encephalopathy dominated by brainstem features and widespread areflexia. Her antiganglioside antibodies and electroencephalography were consistent with Bickerstaff brainstem encephalitis (BBE), and her postmortem examination revealed a predominantly florid brainstem encephalitis and myelitis. Her sputum and throat swabs isolated Haemophilus influenzae and Fusobacterium, respectively, the former being the most probable trigger of BBE. Our patient's death, despite the otherwise good prognosis of the disorder, may reflect the severity of the pathological changes at postmortem or the association of comorbid disorders such as sepsis-associated encephalopathy. Her poor outcome may also be an indication to treat rapidly progressive cases of BBE with more than one immune modulating drug.

How Have Nutrition Practices in the ICU Changed in the Last Decade (2011-2020): A Scoping Review.

Malnutrition is more prevalent in the critically ill than ambulatory patients due to a variety of factors. Strategies employed in the optimization of nutrition practices rely largely on the review of published literature and guidelines. While the last decade was marked by some landmark large randomized controlled trials taking place and some high-quality systematic reviews, it still has left us with many unanswered questions. The evidence generated by these trials can, to a good extent, extrapolate to the developed countries. However, its implementation in developing and third-world countries needs further elaboration and logistical considerations. With this scoping review, we attempt to provide insights into the landmark developments in the decade 2011-2020. Solutions to employ and implement the results of these developments and ways for their corroboration into a larger population are also discussed.

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report.

Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4-6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4). Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss. Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor. Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.

Correction: Histidine protonation controls structural heterogeneity in the cyanobacteriochrome AnPixJg2.

Correction for 'Histidine protonation controls structural heterogeneity in the cyanobacteriochrome AnPixJg2' by Aditya G. Rao et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d0cp05314g.

Histidine protonation controls structural heterogeneity in the cyanobacteriochrome AnPixJg2.

Cyanobacteriochromes are compact and spectrally diverse photoreceptor proteins that bind a linear tetrapyrrole as a chromophore. They show photochromicity by having two stable states that can be interconverted by the photoisomerization of the chromophore. These photochemical properties make them an attractive target for biotechnological applications. However, their application is impeded by structural heterogeneity that reduces the yield of the photoconversion. The heterogeneity can originate either from the chromophore structure or the protein environment. Here, we study the origin of the heterogeneity in AnPixJg2, a representative member of the red/green cyanobacteriochrome family, that has a red absorbing parental state and a green absorbing photoproduct state. Using molecular dynamics simulations and umbrella sampling we have identified the protonation state of a conserved histidine residue as a trigger for structural heterogeneity. When the histidine is in a neutral form, the chromophore structure is homogenous, while in a positively charged form, the chromophore is heterogeneous with two different conformations. We have identified a correlation between the protonation of the histidine and the structural heterogeneity of the chromophore by detailed characterization of the interactions in the protein binding site. Our findings reconcile seemingly contradicting spectroscopic studies that attribute the heterogeneity to different sources. Furthermore, we predict that circular dichroism can be used as a diagnostic tool to distinguish different substates.

Prevalence and Pattern of Dyslipidemia in Diabetes Mellitus Patients Admitted in the Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh.

Patients with Diabetes Mellitus are at high risk of cardiovascular events because of abnormal lipid metabolism. Dyslipidemia is common in patients with Diabetes Mellitus (DM). However; in Bangladesh this issue is not yet properly addressed. The aim of this study is to determine the prevalence and patterns of dyslipidaemia in patients with DM in a divisional city Mymensingh. This cross-sectional study was conducted in randomly selected eligible patients from the indoor registry of the Department of Cardiology, Mymensingh Medical College Hospital (MMCH), Bangladesh from April 2012 to March 2013. A well structured questionnaire and blood investigation for lipid profile and blood sugar were the tools of data collection from 120 randomly selected DM patients registered in the department of cardiology, MMCH. Out of 120 enrolled participants the prevalence of dyslipidemia in DM patients was 86.0%, prevalence of dyslipidemia in males was 88.0% while in females was 85.0% but the difference was not significant (p=0.42). Regarding age group, BMI and duration of DM, there is no significant association exists with dyslipidemia. About half of the studied DM patients have high serum total cholesterol level (50.83%), while 22.5% had low serum HDL-C levels and 35.0% had high serum LDC-C level, most of patients had serum triglyceride levels above normal range (67.5%) and so the common patterns of dyslipidemia in this study were serum triglyceride level followed by total cholesterol. High prevalence of dyslipidemia among diabetes mellitus in Mymensingh city were observed and so the common patterns of dyslipidemia is triglyceride followed by total cholesterol. This study emphasizes the importance of screening of lipid profile as these abnormalities may lead to development of cardiovascular diseases.

Frontiers in Multiscale Modeling of Photoreceptor Proteins.

This perspective article highlights the challenges in the theoretical description of photoreceptor proteins using multiscale modeling, as discussed at the CECAM workshop in Tel Aviv, Israel. The participants have identified grand challenges and discussed the development of new tools to address them. Recent progress in understanding representative proteins such as green fluorescent protein, photoactive yellow protein, phytochrome, and rhodopsin is presented, along with methodological developments.

Status of Plasma Vitamin-D Level in Predicting Adverse In-Hospital Outcome in Patients with First Attack of Acute Myocardial Infarction.

Acute myocardial infarction has many risk factors and etiologies. Different factors are responsible for adverse in-hospital outcome after acute MI. Status of plasma vitamin D level has been found to be a good predictor of future adverse cardiovascular outcomes in patients with acute MI. Plasma vitamin D level has been considered as a potential marker for identifying individuals under risk of CAD and associated events. This study was done to investigate the role of plasma vitamin D level in predicting in-hospital adverse cardiac events in patients with acute MI. This cross sectional descriptive type of study was conducted in the cardiology department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from October 2017 to March 2019. Total 257 patients of first attack of acute MI were included considering inclusion and exclusion criteria. Fasting blood samples were analyzed for plasma vitamin D level. Sample population were grouped at first into two, normal and low vitamin D level, taking 30ng/ml as cut-off value, low vitamin D level is further subdivided into insufficiency (21-29ng/ml), deficiency (10-20ng/ml) and severe deficiency (<10ng/ml). Adverse in-hospital cardiac outcomes were observed. In-hospital adverse outcomes occurred in 42.9% patients having normal vitamin D level (>30ng/ml), 66.2% of patients having vitamin D insufficiency (21-29ng/ml), 78.2% of patients having vitamin D deficiency (10-20ng/ml) and 94.4% patients having severe vitamin D deficiency (<10ng/ml), which was statistically significant (p<0.05). Heart failure (30.3%, 47.7%, 63.6% and 77.8%, p<0.05), cardiogenic shock (12.6%, 27.7%, 34.5% and 33.3%, p<0.05), Arrhythmias (14.3%, 21.5%, 23.6% and 22.2%, p>0.05), death (2.5%, 0%, 3.6% and 11.1%, p>0.05) occurred more in low vitamin D groups. Mean vitamin D level was significantly different between Group I and Group II (42.59±10.08 vs. 18.64±6.54, p<0.0001). Multivariate regression analysis showed vitamin D is an independent predictor of in-hospital adverse cardiac events (p=0.001). Age (p=0.001) and obesity (p=0.048) were also other predictors of in-hospital adverse cardiac events. Low plasma vitamin D level is an important predictor for in-hospital adverse cardiac events in patients hospitalized with first attack of acute MI.

The interplay between chromophore and protein determines the extended excited state dynamics in a single-domain phytochrome.

Phytochromes are a diverse family of bilin-binding photoreceptors that regulate a wide range of physiological processes. Their photochemical properties make them attractive for applications in optogenetics and superresolution microscopy. Phytochromes undergo reversible photoconversion triggered by the Z ⇄ E photoisomerization about the double bond in the bilin chromophore. However, it is not fully understood at the molecular level how the protein framework facilitates the complex photoisomerization dynamics. We have studied a single-domain bilin-binding photoreceptor All2699g1 (Nostoc sp. PCC 7120) that exhibits photoconversion between the red light-absorbing (Pr) and far red-absorbing (Pfr) states just like canonical phytochromes. We present the crystal structure and examine the photoisomerization mechanism of the Pr form as well as the formation of the primary photoproduct Lumi-R using time-resolved spectroscopy and hybrid quantum mechanics/molecular mechanics simulations. We show that the unusually long excited state lifetime (broad lifetime distribution centered at ∼300 picoseconds) is due to the interactions between the isomerizing pyrrole ring D and an adjacent conserved Tyr142. The decay kinetics shows a strongly distributed character which is imposed by the nonexponential protein dynamics. Our findings offer a mechanistic insight into how the quantum efficiency of the bilin photoisomerization is tuned by the protein environment, thereby providing a structural framework for engineering bilin-based optical agents for imaging and optogenetics applications.

Dynamic Properties of the Photosensory Domain of Deinococcus radiodurans Bacteriophytochrome.

Phytochromes are biological photoreceptors found in all kingdoms of life. Numerous physicochemical and spectroscopic studies of phytochromes have been carried out for many decades, both experimentally and computationally, with the main focus on the photoconversion mechanism involving a tetrapyrrole chromophore. In this computational work, we concentrate on the long-scale dynamic motion of the photosensory domain of Deinococcus radiodurans by means of classical all-atom molecular dynamics (MD) simulations. Conventional and accelerated MD methods in combination with two different force fields, CHARMM27 and AMBER ff14SB, are tested in long atomistic simulations to confront the dynamics of monomer and dimer forms. These calculations highlight dissimilar equilibrium conformations in aqueous solutions and, in turn, different large-scale dynamic behaviors of the monomer form vs the dimer form. While the phytochrome in a monomer form tends to close the cavity entailed between the GAF and PHY domains, the opposite trend is predicted for the phytochrome dimer, which opens up as a consequence of the formation of strong salt bridges between the PHY domains of two molecules in water.

Hetero-bimetallic cooperative catalysis for the synthesis of heteroarenes.

Multi-metallic cooperative catalysis has gained a lot of interest in organic synthesis over the past few years exploring various organic transformations. Of all the myriad chemical transformations, multi-metallic cooperative catalysis offers exceptional chemo-, stereo- and regio-selectivities. In recent years, hetero-multi-metallic catalysis has not only been used to synthesise only simpler organic molecules but rather more complex molecules like heteroarenes which include a variety of commercially important molecules. The current review, in this context, emphasises the synthesis of 5- and 6-membered as well as condensed heteroarenes, covering the literature over the last decade. The discussion focusses on the combinations in cooperative catalytic systems in strategies used to achieve selectivity and also highlights the mode of action for the cooperative catalysis leading to the synthesis of a few commercially and biologically relevant heteroarenes. Finally, the review concludes with a brief outlook on the future scope and opportunities in the field of cooperative catalyses and their prospects for providing state-of-the-art solutions for synthetically challenging organic transformations.