Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS: We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.

Psychedelic-assisted psychotherapy to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care.

Psychiatric and existential distress commonly occur in advanced cancer and other serious, life-threatening or end-of-life medical illnesses and are associated with poor medical and psychiatric outcomes. Currently available treatment modalities in this patient population, including medication and psychotherapy, are limited in effectiveness, especially regarding existential distress. The lack of effective psycho-spiritual interventions is a critical shortcoming in palliative care and represents a high unmet need in medicine. In this commentary, we review the rationale of researching and developing psychedelic-assisted psychotherapy as a novel pharmacologic-psychotherapeutic intervention to treat psychiatric and existential distress in life-threatening medical conditions and palliative care. This paper reviews efficacy data from first and second waves of psychedelic research, and future directions for research and implementation science. More rigorous research, especially funded by governments, is needed to assess effectiveness and mechanisms of action of psychedelic therapies to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care. If psychedelic-assisted treatments were made available as approved and prescribable medications in people with serious medical illnesses, it could be a significant development that opens up a pathway for clinical dissemination and public health impact internationally.

Lane-Hamilton syndrome - Is it really a needle in a haystack?

Introduction: The association of pulmonary hemosiderosis with celiac disease (Lane-Hamilton syndrome) is extremely rare. Case Details: A five-year-old female child presented with fever, cough, breathlessness, and pallor for 20 days, without any previous history of recurrent lower respiratory tract infections, tuberculosis, or cardiac disease. There was no history of pica, chronic diarrhea, bleeding, or personal or family history of repeated blood transfusions. She had tachycardia, tachypnea, severe pallor, stunting, rickets, and bilateral fine lung crepitations. Peripheral smear and blood indices revealed dimorphic anemia. Anti-tissue transglutaminase IgA antibody levels were high (>200 U/mL) and the upper gastrointestinal endoscopy with duodenal biopsy confirmed the diagnosis of celiac disease. The child was discharged on a gluten-free diet (GFD) and oral hematinic, but her dietary compliance was poor. Interestingly, the child had persistent bilateral pulmonary infiltrates, which was initially attributed to congestive cardiac failure (CCF), which persisted even despite treatment. HRCT chest revealed interstitial thickening and bilateral alveolar shadows and bronchoalveolar lavage showed a few inflammatory cells. The child was readmitted four times with similar complaints and was given packed red cell transfusions. In the fourth admission, a lung biopsy was done, which revealed extensive pulmonary hemosiderosis. The patient was given a course of oral steroids for 6 weeks, with a gluten-free diet, following which both the anemia and the pulmonary infiltrates resolved. Conclusion: Pulmonary hemosiderosis is an important cause of anemia in cases of celiac disease and may be misdiagnosed as CCF due to severe anemia. A strict GFD, with or without corticosteroids, can reverse the clinical and radiological picture.

Minimally invasive techniques as a first line approach in the management of emphysematous pyelonephritis - A single centre experience.

Context: Emphysematous pyelonephritis (EPN) is a dangerous necrotizing infection of the kidney involving the diabetics with a high case fatality rate. Recent medical literature has shown shifting of treatment strategy from conventional radical approach to minimally invasive approach. Aims: The aim of our study was to assess the role of minimally invasive stepwise decompression techniques in the management of EPN and preservation of the renal unit. Settings and Design: : This was a retrospective observational study conducted from June 2017 to April 2020 at a tertiary care centre. Material and Methods: We reviewed the hospital online records of 18 patients diagnosed with EPN for patient demographics, clinical profiles, co-morbidities, laboratory and, radiological investigations, surgical interventions performed and the outcomes. The severity of EPN was graded as per the Huang classification. Patients underwent surgical interventions as per the treatment protocol and response was assessed. Statistical Analysis Used: Descriptive statistics was applied. Results: Diabetes mellitus was present in 15 (83.3%) patients along with urinary tract obstruction in 8 (44.4%) patients. Flank pain (77.7%) was the most common presenting clinical feature while Escherichia coli (55.5%) were the most common causative organism. Most patients (50%) had Type- II EPN, all of which were managed successfully by minimally invasive procedures. In total seventeen patients (94.4%) responded well while one patient (5.5%) underwent nephrectomy with no mortality. Conclusions: Renal salvage in EPN requires multidisciplinary approach including the initial medical management followed by properly selected stepwise decompressive surgical techniques. Conservative management and decompression techniques have shown to improve patient's outcome, reducing the traditional morbidity associated with nephrectomy.

Effects of plant age on performance of the tropical perennial fodder grass, Cenchrus ciliaris L. subjected to elevated ultraviolet-B radiation.

Abiotic stress, notably high ultraviolet-B (eUV-B), limit growth and productivity of many crop plants, but information on response of forage grasses to eUV-B radiation is rather limited. The present study was therefore conducted to increase our understanding of differential age-related responses on growth, metabolism and fodder quality of Cenchrus ciliaris-3108 (Buffel grass) to elevated UV-B (eUV-B: 7.2 kJ·m-2 ·day-1 ). Plant growth at both growth stages was notably reduced in response to eUV-B, except for the number of nodes and tillers at vegetative and reproductive stages. At anthesis, tillering increased due to the perennial habit of this plant, but leaf senescence reduced the number of leaves per tiller. Unlike ambient UV-B, eUV-B at the vegetative stage resulted in diversion of photosynthate for the formation of secondary metabolites (tannins and phenolics), providing dual protection from photooxidative damage and from herbivory. The forage biomass as well as quality showed a marked decline under eUV-B and relative nutritive value was reduced at both growth stages.

A Rare Pigmented Lesion of the Eyelid.

This study aims to report a rare case of melanoacanthoma of the eyelid. Melanoacanthoma is very rare variant of seborrheic keratosis presenting as a rare benign pigmented lesion composed of both melanocytes and keratinocytes usually presenting over the head, neck, and trunk of elderly people. A 61-year-old female presented with 8 mm × 4 mm × 3 mm brownish black mass in her right lower lid for the past 4 years associated with itching. Clinical differential diagnosis of seborrheic keratosis and nevus was offered. The patient underwent shave biopsy, and biopsy tissue was sent for histopathological examination. A diagnosis of melanoacanthoma was made on histopathology. Melanoacanthoma of the eyelid is a rare entity, and one should consider in differential diagnosis of pigmented lesion of the eyelid mass.

Comparative evaluation of a single 2.0-mm AO locking reconstruction plate with conventional miniplate osteosynthesis for treatment of linear non-comminuted fractures of symphysis and parasymphsis region of the mandible.

The objective of the study was to evaluate and compare the relative efficacy of treating linear non-comminuted mandibular fracture of symphysis and parasymphysis region using single 2.0-mm AO locking reconstruction plate or using two conventional miniplates. In this study, 80 patients of symphysis or parasymphysis fracture were divided randomly in two equal groups and treated with open reduction and internal fixation using two 2.5-mm miniplates or with a single 2.0-mm AO locking reconstruction plate. Operating time in case of open reduction and fixation using a single 2.0-mm locking reconstruction plate was significantly less when compared to open reduction and fixation using two conventional miniplates. Both groups showed satisfactory fracture reduction and healing. No postoperative malocclusion was noted, and both groups showed comparable improvement in masticatory efficiency. In conclusion, fracture fixation using a single 2.0-mm AO locking reconstruction plate without use of a second plate at the superior border for treatment of linear non comminuted mandibular fracture in symphysis and parasymphysis region gives comparable results as with treatment by conventional miniplate system and provides significant savings in operating time, ease of use and decrease in amount of hardware incorporated in the body.

Some facts on south asian schistosomiasis and need for international collaboration.

In this review, we are discussing South Asian schistosomiasis; more specifically species which are responsible for schistosomiasis in India or South Asia -Schistosoma indicum, S. spindale, S. nasale, S. incognitum, S. gimvicum (S.haematobium), Bivitellobilharzia nairi, Orientobilharzia bomfordi, O. dattai, O. turkestanicum and O.harinasutai, their survival strategies such as mild pathology to the host, producing low egg number and utilizing fresh water snails (Indoplanorbis exustus and Lymnaea luteola) in stagnant water bodies like ponds, lakes, ditches, low laying areas, marshy lands and rice fields. Presently, correct identification of blood fluke species, their immature stages, male schistosomes and their intermediate host details like strain variations, susceptibilities, ecologies are not well studied. Species like B. nairi, O. bomfordi, O. harinasutai (Lymnaea rubiginosa intermediate host for O.harinasutai in Thailand) are also not well studied. Moreover, snail species like Oncomalania spp are not from South Asia, but species of Tricula or Neotricula are reported from this geography, which gives indications of S. mekongi like blood fluke presence in the area. Although in humans, cercarial dermatitis is rampant in rural population with occasional reporting of schistosome eggs in stools, human schistosomiasis is considered absent from this region, despite finding a foci (now dead) of urinary schistosomiasis in Gimvi village of Ratnagiri district, Maharashtra, India. There is great difficulty in diagnosing the infection in man and animals due to low egg production, hence development of a single step antigen detection test is the need of the hour. Interestingly, lethal effect of praziquantel was seen against S.haematobium and S.mansoni. However, this drug failed to cause significant reduction of S. incognitum and S. spindale experimentally suggesting some differences in the biology of two groups of the schistosomes. Triclabendazole showed adulticidal effect at a dose rate of 20 mg/kg body against female schistosome worms, but at lower dose (10 mg/kg body wt) of the drug, a dose that is used in treating bovine fascioliasis, it is providing chances of drug resistance of the persisting schistosomes against triclabendazole. Though the South Asian institutes have all the facilities to tackle issues related to existing schistosomes, it is recommended to develop an international collaboration by establishing an international centre on schistosomiasis in India.

The evolution of artificial hair implantation.

From the beginning, artificial hair implantation has aroused a lot of interest, sometimes controversial, in the field of hair restoration. The artificial fiber must be of high quality and biocompatible. Biofibre® is a very fine fiber having diameter of 80 m. The standard length of this fiber is 15 or 30 cm, to satisfy multiple patient requests. They are available in 13 colors and 3 different shapes (straight, wavy and curly). Artificial hair implant is indicated in all (male and female) cases of androgenetic alopecia, especially for those who show dismal response to medical therapies and have poor donor area supply for hair transplantation. It has also shown good results to treat scars. One hundred thirty-three cases of androgenetic alopecia were treated with Biofibre® and followed-up for 3 years. A clinical evaluation was carried out after 1 month, 4 months and every other 4 months after the implant. The fiber loss was no more than 10% per year in 91.4% of the cases, 15% in 7.8% of the cases and 20% in 0.8% of the cases. 96.2% of patients declared themselves to be satisfied with the result of the implant while 3.8% declared to be not satisfied. To conclude, modern artificial hair implantation can be considered a safe and easy mode of hair restoration, for male and female patients, especially in donor depleted cases or when an immediate aesthetic result is required.

When potion becomes poison! A case report of flecainide toxicity.

We report a 48-day-old female infant, who developed cardiac conduction abnormalities and seizures secondary to supratherapeutic doses of oral flecainide. Flecainide was started in this infant for treatment of supraventricular tachycardia. The drug was withdrawn with successful normalization of the QRS complex and no further recurrence of seizures. The Naranjo probability score for adverse drug reaction was 8, making the causality "probable." The case restates an important message that physicians should be aware of the side effects of the drugs that they prescribe, especially of those drugs which have a narrow therapeutic window.

Cross-sectional imaging of aortic infections.

Aortic infections are uncommon clinical entities, but are associated with high rates of morbidity and mortality. In this review, we focus on the cross-sectional imaging appearance of aortic infections, including aortic valve endocarditis, pyogenic aortitis, mycotic aneurysm and aortic graft infections, with an emphasis on CT, MRI and PET/CT appearance. Teaching Points • Aortic infections are associated with high morbidity and mortality. • CT, MRI and FDG PET/CT play complementary roles in aortic infection imaging. • Radiologists should be vigilant for aortic infection manifestations to ensure timely diagnosis.

Progressive Disseminated Histoplasmosis with Coomb's Positive Hemolytic Anemia in an Immunocompetent Host.

Progressive Disseminated Histoplasmosis (PDH) is mainly described in immuno-compromised individuals and rare in immuno-competent subjects. Here we report a case of progressive disseminated histoplasmosis with Comb's positive hemolytic anemia, which is infrequently reported from a country like India where histoplasmosis is not an endemic mycosis.

"FISHed" out the diagnosis: A case of DiGeorge syndrome.

Our patient presented with congenital heart disease (CHD: Tetralogy of Fallot), hypocalcemia, hypoparathyroidism, and facial dysmorphisms. Suspecting DiGeorge syndrome (DGS), a fluorescence in situ hybridization (FISH) analysis for 22q11.2 deletion was made. The child had a hemizygous deletion in the 22q11.2 region, diagnostic of DGS. Unfortunately, the patient succumbed to the heart disease. DGS is the most common microdeletion syndrome, and probably underrecognized due to the varied manifestations. This case stresses the importance of a detailed physical examination and a high index of suspicion for diagnosing this genetic condition. Timely diagnosis can help manage and monitor these patients better and also offer prenatal diagnosis in the next pregnancy.

Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells--PC12.

Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 µM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.

Sphincter of Oddi disorder (SOD): Is it necessary to investigate and treat?

Sphincter of Oddi disorder (SOD) is a part of functional gastrointestinal disorder which is a non-calculous obstructive disorder. This disease is more common in middle-aged women with a prevalence of around 1.5% but in patients with post-cholecystectomy syndrome (PCS) the prevalence rate is markedly higher (9-55%). This high variability maybe attributed to lack of uniformity in patient selection criteria, definition of SOD, and the diagnostic method used. Abdominal pain is the most common symptom occurring due to obstruction at the SO leading to ductal hypertension, ischemia from spastic contraction and hypersensitivity of papilla. Clinical diagnosis of SOD can be achieved by Rome III criteria. Various classifications are used (Milwaukee billiary and modified Milwaukee group classification) for billiary and pancreatic SOD. Not a single non-invasive method is diagnostic. Sphincter of Oddimanometry (SOM) is the gold standard method for evaluating and deciding the management of an SOD patient. The symptomatic relief rate varies from 55% to 95%, so risk-benefit ratio should be evaluated with each patient.

Steady state temperature distribution in dermal regions of an irregular tapered shaped human limb with variable eccentricity.

The investigators in the past have developed some models of temperature distribution in the human limb assuming it as a regular circular or elliptical tapered cylinder. But in reality the limb is not of regular tapered cylindrical shape. The radius and eccentricity are not same throughout the limb. In view of above a model of temperature distribution in the irregular tapered elliptical shaped human limb is proposed for a three dimensional steady state case in this paper. The limb is assumed to be composed of multiple cylindrical substructures with variable radius and eccentricity. The mathematical model incorporates the effect of blood mass flow rate, metabolic activity and thermal conductivity. The outer surface is exposed to the environment and appropriate boundary conditions have been framed. The finite element method has been employed to obtain the solution. The temperature profiles have been computed in the dermal layers of a human limb and used to study the effect of shape, microstructure and biophysical parameters on temperature distribution in human limbs. The proposed model is one of the most realistic model as compared to conventional models as this can be effectively employed to every regular and nonregular structures of the body with variable radius and eccentricity to study the thermal behaviour.

Responses of Beta vulgaris exposed to cadmium and zinc through soil drenching.

The present study investigates the responses of Indian palak (Beta vulgaris L. cv. All Green H1) exposed to cadmium (Cd) and zinc (Zn) at growth, biochemical and physiological levels. The results revealed that Cd and Zn accumulation was higher in shoots as compared to the roots of B. vulgaris plants. The increased application rates of Zn in combination with Cd significantly reduced the accumulation of Cd in below and above ground parts of B. vulgaris, whereas it increased Zn accumulation. Treatments of B. vulgaris with Cd and Zn individually or in combination significantly reduced the leaf area, biomass, photosynthetic pigments, photosynthetic rate, Fv/Fm ratio and protein contents at p < 0.05. Contrary to this, lipid peroxidation, ascorbic acid, proline and thiol contents and peroxidase activity increased significantly as compared to control at p < 0.05. The results also revealed that the combined effectof Cd and Zn were more pronounced at higher concentrations as compared to other treatments. Thus, the present study suggests that Zn may be applied to Cd contaminated field to reduce Cd accumulation in plants. However, finding of a suitable dose and toxicity level of Zn must be worked out further its application.

MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure.

In the face of competing tyrosine kinase inhibitors (TKIs), identification of chronic myeloid leukemia (CML) patients expecting favorable response to second-line treatment is warranted. At the time of imatinib resistance, the investigation of multidrug-resistance protein 1 (MDR1) and BCR-ABL yielded the following results: (i) Patients with high MDR1 transcript levels showed superior response at 48 months as compared with low-level MDR1 patients: major molecular response (MMR) in 41% vs 16% (P=0.014), complete cytogenetic response (CCyR) in 58% vs 39% (P=0.044), and progression-free survival (PFS) in 67% vs 46% (P=0.032). (ii) Patients with BCR-ABL(IS) <28% achieved higher MMR rates (48% vs 21%, P=0.009). (iii) PFS at 48 months was associated with in vitro resistance of BCR-ABL kinase domain mutations: 63% (no mutation) vs 61% (sensitive, intermediately sensitive or unknown IC50 (median inhibitory concentration)) vs 23% (resistant, P=0.01). (iv) Single-nucleotide polymorphisms (SNPs) at positions 1236 and 2677 were associated with higher MDR1 expression in comparison to wild type. (v) Nilotinib was able to impede proliferation of MDR1-overexpressing imatinib-resistant cells. High MDR1 gene expression might identify patients whose mode of imatinib resistance is essentially determined by increased efflux activity of MDR1 and therefore can be overcome by second-line nilotinib treatment.