Environmental, socioeconomic, and health factors associated with gut microbiome species and strains in isolated Honduras villages.

Despite a growing interest in the gut microbiome of non-industrialized countries, data linking deeply sequenced microbiomes from such settings to diverse host phenotypes and situational factors remain uncommon. Using metagenomic data from a community-based cohort of 1,871 people from 19 isolated villages in the Mesoamerican highlands of western Honduras, we report associations between bacterial species and human phenotypes and factors. Among them, socioeconomic factors account for 51.44% of the total associations. Meta-analysis of species-level profiles across several datasets identified several species associated with body mass index, consistent with previous findings. Furthermore, the inclusion of strain-phylogenetic information modifies the overall relationship between the gut microbiome and the phenotypes, especially for some factors like household wealth (e.g., wealthier individuals harbor different strains of Eubacterium rectale). Our analysis suggests a role that gut microbiome surveillance can play in understanding broad features of individual and public health.

Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases.

The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the host's overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.

Segatella copri strains adopt distinct roles within a single individual's gut.

Segatella copri is a dominant member of individuals' gut microbiomes worldwide, especially in non-Western populations. Although metagenomic assembly and genome isolation have shed light on the genetic diversity of S. copri, the lack of available isolates from this clade has resulted in a limited understanding of how members' genetic diversity translates into phenotypic diversity. Within the confines of a single gut microbiome, we have isolated 63 strains from diverse lineages of S. copri. We performed comparative analyses that exposed differences in cellular morphologies, preferences in polysaccharide utilization, yield of short-chain fatty acids, and antibiotic resistance across isolates. We further show that exposure to S. copri lineages either evokes strong or muted transcriptional responses in human intestinal epithelial cells. Our study exposes large phenotypic differences within related S. copri isolates, extending this to host-microbe interactions.

Local Flaps in Breast-Conserving Surgery in Early Breast Cancer Patients: Armamentarium for Breast Surgeon.

To describe the technique and outcome of local perforator arteries advancement flap in breast-conserving surgeries (BCS) in patient of early breast cancer as our initial experience and review of literature on it. Patients who underwent (BCS) with local perforator artery flap reconstruction were reviewed in terms of their clinical, surgical, and post-operative follow-up details after taking written and informed consent. We have described 4 patients of early breast cancer out of which one patient was post-NACT while 3 were for upfront BCS. We have performed LICAP in 2 patients, AICAP in 1 patient, and IMAP in one patient, depending on the location of primary tumors. None of the patients had any major or minor surgical complications in the post-operative period and drains were removed on post-operative day 2. All patients received post-operative radiotherapy and tolerated well without any loco-regional complications. Patients are in routine follow-up with cosmetic satisfaction without any local recurrence over 1 year. The main advantages of pedicled perforator flaps are well-vascularized tissue, spares underlying muscle leading to lesser donor site morbidity like muscle function and seroma formation, easily reach the breast area with good match in terms of skin and subcutaneous tissue, faster recovery, and shorter learning curve in comparison to free flaps. Knowledge and skill about these flaps will help surgeon to give better surgical outcomes and satisfaction to patients.

Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases.

The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the host's overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.

Oxidative treatment of micropollutants present in wastewater: A special emphasis on transformation products, their toxicity, detection, and field-scale investigations.

Micropollutants have become ubiquitous in aqueous environments due to the increased use of pharmaceuticals, personal care products, pesticides, and other compounds. In this review, the removal of micropollutants from aqueous matrices using various advanced oxidation processes (AOPs), such as photocatalysis, electrocatalysis, sulfate radical-based AOPs, ozonation, and Fenton-based processes has been comprehensively discussed. Most of the compounds were successfully degraded with an efficiency of more than 90%, resulting in the formation of transformation products (TPs). In this respect, degradation pathways with multiple mechanisms, including decarboxylation, hydroxylation, and halogenation, have been illustrated. Various techniques for the analysis of micropollutants and their TPs have been discussed. Additionally, the ecotoxicity posed by these TPs was determined using the toxicity estimation software tool (T.E.S.T.). Finally, the performance and cost-effectiveness of the AOPs at the pilot scale have been reviewed. The current review will help in understanding the treatment efficacy of different AOPs, degradation pathways, and ecotoxicity of TPs so formed.

The study on the prevalence of Mongolian spots in the neonates.

Background: Mongolian Spots (MS) generally exist at the time or under the first few weeks of the neonate life-cycle, often considered a birthmark, characterized by hyper-pigmented marks especially bluish-black hue that cannot vanish easily and are generally found on the lumbosacral region. As this MS is reminiscent of bruises and appears to be caused by abuse, this may raise questions about the possibility of abuse. Hence, it is significant to identify MS bruises. The objective of the study was to assess the prevalence of MS in neonates by using the parameters like location, method of delivery, gestational age, and, weight at birth. Methodology: 500 neonates were enrolled in the study for the evaluation of the prevalence of Mongolian spots. The study design was cross-sectional, observational, and conducted for two and a half years. The neonate's whole skin surface, including the hand palms, scalps and soles, mucous membranes, genitalia, hair, and nails, was inspected in adequate light. The changes were seen (physiological and pathological) over the skin, so the details were reviewed, analyzed, and documented. Photographic records were kept to document the study. Descriptive statistics were analyzed by t-test and Chi-square test and the inferential statistics were analyzed by proportions and Chi-square test. Results: From the 500 neonates, 408 (81.6%) were reported to have Mongolian spots. Based on the site of locations 337 (82.60%) neonates were found with spots maximum on the sacrococcygeal area and rarely on the extremities 4 (0.98%). 221 (54.1%) were found with normal vaginal delivery, and males have more predominance 247 (60%). Based on the gestational age full term was 366 (89.71%), with the birth at a weight of more than 2.5 kg found in 349 (85.54%). Conclusion: The study concluded that the maximum number of neonates had been found with Mongolian spots and it is very common among neonates. This study will enlighten the awareness of the physician to distinguish the other lesions from other cutaneous skin conditions. The only drawbacks of this research study are a smaller sample size and limited study duration. The study of diameter, size, and dimensions of spots are not included. More intervention studies are required to compare MS with other skin conditions and their therapies. Further research is required for the study of the dimensions of marks on the neonate's body.

Puzzling painful nodules on back: a case report.

Cutaneous leiomyomas are known to arise from three locations viz, arrector pili muscle, dartos muscle in the scrotal sac, and smooth muscle layer of blood vessels. Cutaneous piloleiomyoma (arising from arrector pili) is an uncommon benign skin tumor presenting clinically as a single or numerous painful nodules. They can either appear diffuse or zosteriform/segmental in rare cases. We report an unusual case of multiple tender papulonodular lesions on the right infrascapular region. Histology from one of the nodules showed a dermal tumor consisting of interlacing fascicles of spindle cells, consistent with the diagnosis of piloleiomyoma. We prescribed our patient with oral calcium channel blocker, amlodipine, to provide symptomatic relief from pain and which can be considered used it to treat similar cases.

Advancements of sequencing batch reactor for industrial wastewater treatment: Major focus on modifications, critical operational parameters, and future perspectives.

Industrial wastewater discharge has increased manifolds over the last few decades. Efficient industrial wastewater treatment is mandatory to meet stringent discharge regulations. Biological treatment systems, such as the sequencing batch reactor (SBR) are generally employed for domestic wastewater treatment. However, low infrastructure and energy requirements, as well as low footprint, make SBR a prominent technique to treat industrial wastewater. In the present review, the feasibility of SBR to treat wastewater generated from industries, such as textile, pulp and paper, pharmaceutical, tannery, etc., has been discussed. The factors affecting the treatment efficacy of the SBR in terms of organics and nutrient removal have also been investigated. It has been observed that the SBR system is effective for industrial wastewater treatment as it is easy to operate, resistant to shock loads, and can retain high biomass concentrations. The modifications to the conventional SBR, such as sludge granulation, the addition of bio-film carriers, and the incorporation of adsorbents, salt-tolerant microbes, and coagulants have been discussed. Further, various novel combinations of SBR with the other advanced treatment technologies, such as Fenton, membrane-based process, and electrochemical process have shown enhanced removal of various conventional and recalcitrant pollutants. The current review also accentuates the sustainability aspects of SBR technology to treat industrial wastewater which may be beneficial for researchers and engineers working in this field.

A review on electrocoagulation process for the removal of emerging contaminants: theory, fundamentals, and applications.

Electrocoagulation (EC) is an excellent and promising technology in wastewater treatment, as it combines the benefits of coagulation, flotation, and electrochemistry. During the last decade, extensive researches have focused on removal of emerging contaminants by using electrocoagualtion, due to its several advantages like compactness, cost-effectiveness, efficiency, low sludge production, and eco-friendness. Emerging contaminants (ECs) are micropollutants found in trace amounts that discharging into conventional wastewater treatment (WWT) plants entering surface waters and imposing a high threat to human and aquatic life. Various studies reveal that about 90% of emerging contaminants are disposed unscientifically into water bodies, creating problems to public health and environment. The studies on removal of emerging contaminants from wastewater are by global researchers are critically reviewed. The core findings proved that still more research required into optimization of parameters, system design, and economic feasibility to explore the potential of EC combined systems. This review has introduced an innovative collection of current knowledge on electro-coagulation for the removal of emerging contaminants.

A large-scale computational screen identifies strong potential inhibitors for disrupting SARS-CoV-2 S-protein and human ACE2 interaction.

SARS-CoV-2 has infected millions of individuals across the globe and has killed over 2.7 million people. Even though vaccines against this virus have recently been introduced, the antibody generated in the process has been reported to decline quickly. This can reduce the efficacy of vaccines over time and can result in re-infections. Thus, drugs that are effective against COVID-19 can provide a second line of defence and can prevent occurrence of the severe form of the disease. The interaction between SARS-CoV2 S-protein and human ACE2 (hACE2) is essential for the infection of the virus. Thus, drugs that block this interaction could potentially inhibit SARS-CoV-2 infection into the host cells. To identify such drugs, we first analyzed the recently published crystal structure of S-protein-hACE2 complex and identified essential residues of both S-protein and hACE2 for this interaction. We used this knowledge to virtually dock a drug library containing 4115 drug molecules against S-protein for repurposing drugs that could inhibit binding of S-protein to hACE2. We identified several potential inhibitors based on their docking scores, pharmacological effects and ability to block residues of S protein required for interaction with hACE2. The top inhibitors included drugs used for the treatment of hepatitis C (velpatasvir, pibrentasvir) as well as several vitamin D derivatives. Several molecules obtained from our screen already have good experimental support in published literature. Thus, we believe that our results will facilitate the discovery of an effective drug against COVID-19. Communicated by Ramaswamy H. Sarma.

A Clinico-trichological Study of Female Androgenetic Alopecia.

BACKGROUND: Female Androgenetic Alopecia (FAGA) is one of the most common cause of diffuse scalp hair loss in women. FAGA is insidious in onset, gradually progressive, non scarring alopecia. Trichoscopy is a newly developed non invasive, objective, bed side analytical method of hair imaging based on video dermoscopy of scalp. The objective of this study is to study the clinical features of female androgenetic alopecia, to study the trichoscopic features in patients of female androgenetic alopecia and to correlate the trichoscopic features according to clinical grade of female androgenetic alopecia. METHODS: Study enrolled 50 females with FAGA and 50 normal females. FAGA cases were divided into subgroups according to sinclair scale. Laboratory investigations including hemoglobin level, triiodothyronine (T3), thyroxine (T4) thyroid stimulating hormone (TSH) and serum ferritin level were carried out in both cases and controls. After clinical diagnosis, trichoscopic examination was done and categorised using Diagnostic Criteria set by Rakowska A. et al and trichoscopic findings were coorelated with clinical grades. RESULTS: >4 yellow dots in frontal area , >2:1 ratio of single hair units (frontal: occiput) & >3:1 ratio of hair with perifollicular discoloration (frontal: occiput) are mainly seen in late stages of FAGA i.e. grade 4 & 5 and >1.5:1 ratio of vellus hairs (frontal :occiput) in early stages i.e. grade 2 & 3 while lower mean hair thickness in frontal area & > 10% thin hairs in frontal area are seen in all stages of FAGA Conclusion: Trichoscopy not only confirms the diagnosis by assessing the trichoscopic features of FAGA but also coorelates them with clinical severity. And as the age increases, grade of clinical severity increases. Not necessarily hemoglobin, thyroid and serum ferritin levels will be dearranged in FAGA cases. LIMITATION: The study is done on few number of patients. Further studies needs to be done to validate results.

A novel method to identify and correct asymmetry of dumbbells in a multi-cell elliptical superconducting cavity.

Raja Ramanna Centre for Advanced Technology (RRCAT) has an ongoing program to develop 650 MHz, 5-cell elliptical superconducting RF (SCRF) cavities under the Indian Institutes and Fermilab Collaboration. The elliptical multi-cell SCRF cavity fabrication process involves forming of half-cells and their precise machining and joining by electron beam welding to form end groups and dumbbells, which are then joined to make the final cavity. To ensure that the final welded cavity achieves physical lengths and resonant frequencies within design tolerance and has good field flatness, the measurement and correction of resonant frequency are carried out for dumbbells and end groups. A novel method to identify the frequency of individual half-cells in a dumbbell cavity and a dedicated tuning fixture to correct them had been developed. The paper details the RF characterization and correction procedure employed during fabrication of the first six 650 MHz cavities at RRCAT.

Screening of Latent Tuberculous Infection (LTBI) before Starting Anti-Tumor Necrosis Factor Therapy in Patients with Psoriasis: A Primer for Clinical Dermatologist.

Anti-tumor necrosis agents are being increasingly used in the management of moderate to severe psoriasis. Therapy with antitumor necrosis factor alpha (TNF-α) agents is being fraught with reactivation of latent tuberculosis infection (LTBI). This paper addresses the intricate relation between LTBI and anti-TNF-α agents and provides working guidelines for screening of LTBI and its management before prescribing anti-TNF-α therapy in patients with psoriasis.

Association of Dengue Virus and Leptospira Co-Infections with Malaria Severity.

Plasmodium infections are co-endemic with infections caused by other agents of acute febrile illnesses, such as dengue virus (DENV), chikungunya virus, Leptospira spp., and Orientia tsutsugamushi. However, co-infections may influence disease severity, treatment outcomes, and development of drug resistance. When we analyzed cases of acute febrile illness at the All India Institute of Medical Sciences, New Delhi, India, from July 2017 through September 2018, we found that most patients with malaria harbored co-infections (Plasmodium mixed species and other pathogens). DENV was the most common malaria co-infection (44% of total infections). DENV serotype 4 was associated with mild malaria, and Leptospira was associated with severe malaria. We also found the presence of P. knowlesi in our study population. Therefore, in areas with a large number of severe malaria cases, diagnostic screening for all 4 DENV serotypes, Leptospira, and all Plasmodium species should be performed.

Superior Resonant Nanocavities Engineering on the Photonic Crystal-Coupled Emission Platform for the Detection of Femtomolar Iodide and Zeptomolar Cortisol.

Although luminescence spectroscopy has been a promising sensing technology with widespread applications in point-of-care diagnostics and chem-bio detection, it fundamentally suffers from low signal collection efficiency, considerable background noise, poor photostability, and intrinsic omnidirectional emission properties. In this regard, surface plasmon-coupled emission, a versatile plasmon-enhanced detection platform with >50% signal collection efficiency, high directionality, and polarization has previously been explored to amplify the limit of detection of desired analytes. However, high Ohmic loss in metal-dependent plasmonic platforms has remained an inevitable challenge. Here, we develop a hybrid nanocavity interface on a template-free and loss-less photonic crystal-coupled emission (PCCE) platform by the quintessential integration of high refractive index dielectric Nd2O3 "Huygens sources" and sharp-edged silver nanoprisms (NPrs). While efficient forward light scattering characteristics of Nd2O3 nanorods (NRs) present 460-fold emission enhancements in PCCE, the tunable localized plasmon resonances of NPrs display high electromagnetic field confinement at sharp nanotips and protrusions, boosting the enhancements 947-fold. The judicious use of silver NPr (AgNPr) metal-Nd2O3 dielectric hybrid resonances in conjugation with surface-trapped Bloch surface waves of the one-dimensional photonic crystal (1DPhC) displayed unprecedented >1300-fold enhancements. The experimental results are validated by excellent correlations with numerical calculations. The multifold hotspots generated by zero and nonzero nanogaps between the coassembly of NPrs, NRs, and 1DPhCs are used for (i) determination of hyper and hypothyroidism levels through monitoring the concentration of iodide (I-) ions and (ii) single-molecule detection (zeptomolar) of the stress hormone, cortisol, through the synthesized cortisol-rhodamine B conjugate obtained using a simple esterification reaction.

Study of oral tranexamic acid, topical tranexamic acid, and modified Kligman's regimen in treatment of melasma.

BACKGROUND: Melasma is a pigmentary disorder affecting mainly face . Various treatment modalities available as topicals, superficial chemical peels and lasers but none till date gives promising results, until date quest for the best treatment modality is on. AIM: To study the effect of oral and topical Tranexamic acid (TXA) and modified Kligman's regimen in treatment of melasma. METHOD: Patients having melasma were enrolled after consent for voluntary participation. A detailed history and clinical examination was done. Total 60 patients were enrolled and randomized in three groups, 20 received oral TXA 250 mg twice daily, 20 topical TXA and 20 received modified Kligman's regimen for 8 weeks along with sunscreen MASI(Melasma area severity index) was calculated at baseline, at end of 4 & 8 weeks. MASI score was compared with that at the end of the study. Based on reduction in mean MASI the therapeutic response was graded. Pre and post treatment photographs was also compared. Statistical analysis done by using student square T test , ANOVA And TUKEY test. RESULTS: Reduction in MASI score was observed in all the groups but greater reduction in MASI score with modified Kligman's regimen by 30% followed with oral TXA by 25% reduction and least with topical TXA by 5%. CONCLUSION: Although modified Kligman's regimen is comparatively more efficient but due to its side effects in long term usage oral tranexamic acid could be a promising therapeutic approach for melasma.

Cell Cycle-Dependent Flagellar Disassembly in a Firebug Trypanosomatid Leptomonas pyrrhocoris.

Current understanding of flagellum/cilium length regulation focuses on a few model organisms with flagella of uniform length. Leptomonas pyrrhocoris is a monoxenous trypanosomatid parasite of firebugs. When cultivated in vitro, L. pyrrhocoris duplicates every 4.2 ± 0.2 h, representing the shortest doubling time reported for trypanosomatids so far. Each L. pyrrhocoris cell starts its cell cycle with a single flagellum. A new flagellum is assembled de novo, while the old flagellum persists throughout the cell cycle. The flagella in an asynchronous L. pyrrhocoris population exhibited a vast length variation of ∼3 to 24 µm, casting doubt on the presence of a length regulation mechanism based on a single balance point between the assembly and disassembly rate in these cells. Through imaging of live L. pyrrhocoris cells, a rapid, partial disassembly of the existing, old flagellum is observed upon, if not prior to, the initial assembly of a new flagellum. Mathematical modeling demonstrated an inverse correlation between the flagellar growth rate and flagellar length and inferred the presence of distinct, cell cycle-dependent disassembly mechanisms with different rates. On the basis of these observations, we proposed a min-max model that could account for the vast flagellar length range observed for asynchronous L. pyrrhocoris. This model may also apply to other flagellated organisms with flagellar length variation.IMPORTANCE Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme stability and lack of ciliary disassembly/absorption during the cell cycle. This is different from cilia in Chlamydomonas and mammalian cells, which undergo complete absorption prior to cell cycle initiation. In this study, we examined flagellum duplication during the cell cycle of Leptomonas pyrrhocoris With the shortest duplication time documented for all Trypanosomatidae and its amenability to culture on agarose gel with limited mobility, we were able to image these cells through the cell cycle. Rapid, cell cycle-specific flagellum disassembly different from turnover was observed for the first time in trypanosomatids. Given the observed length-dependent growth rate and the presence of different disassembly mechanisms, we proposed a min-max model that can account for the flagellar length variation observed in L. pyrrhocoris.

Advanced colorectal carcinoma with testicular metastasis in an adolescent: a case report.

BACKGROUND: Colorectal carcinoma in the pediatric age group is rare and tends to be very aggressive and present late, due to which it has a very poor prognosis. It may present with distant metastasis; however, metastasis to the testes is very rare and signifies an advanced stage of the disease. Surgery is the only effective modality to cure patients with localized colorectal carcinomas. However, statistics show a higher incidence of unresectable disease and a higher metastasis rate in childhood colorectal carcinomas. We present a case of advanced colorectal carcinoma with testicular metastasis in an adolescent. CASE PRESENTATION: A 15-year-old Indian Hindu boy presented to surgical emergency with signs and symptoms of intestinal obstruction. He also had a history of passing blood and mucus per rectum. On examination he had abdominal distension. On digital rectal examination, a circumferential proliferative growth was felt 1 cm above the anal verge. On scrotal examination, a small nodule was felt in his right testis. In view of intestinal obstruction, he was taken into our emergency operation theater and a diverting loop sigmoid colostomy was performed to relieve the obstruction. A punch biopsy from anorectal growth was taken which suggested signet ring cell adenocarcinoma. Contrast-enhanced computed tomography of his chest, abdomen, and pelvis showed advanced colorectal carcinoma with distant metastasis. Ultrasonography of his testes showed a hypoechoic nodule in the right testis from which a needle aspiration biopsy was done which revealed metastatic adenocarcinoma. CONCLUSIONS: Childhood colorectal carcinomas have a very poor prognosis due to their aggressive nature and late presentation. In spite of all the advances in diagnosis and treatments, the overall long-term survival is still dismal in these patients. Due to the rarity of this disease, screening is not recommended for individuals under the age of 50. Thus, to improve outcome, early diagnosis and treatment is paramount. For that to happen, awareness needs to be created regarding pediatric colorectal carcinoma and its signs and symptoms.