Microbiota-Short Chain Fatty Acid Relationships and Microbial Substrate Preferences Vary Across the Spectrum of Irritable Bowel Syndrome (IBS).

Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers. KEY MESSAGES: What is already known on this topic: The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. What this study adds: We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. How this study might affect research, practice or policy: Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.

Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome.

INTRODUCTION: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.

Transverse divergent dislocation of elbow in a child: a case report and review of current literature.

We present a case report on transverse divergent dislocation of the elbow, highlighting the spatial relation among the proximal radius, ulna, and distal humerus in this rare pediatric elbow injury and reasons leading to misinterpretation of radiographs. Elbow dislocation is a rare injury in children. It comprises only 6% of pediatric elbow injuries. Most pure dislocations are posterior, but they can occur in any direction. Divergent dislocation of the elbow is a subgroup of posterior dislocation, which is extremely rare. It is important that the pediatric emergency physician is aware, able to identify, and manage this injury. It is defined as a specific elbow dislocation in which the distal humerus is forced between the proximal radius and ulna, resulting in the divergence of the proximal forearm bones. Joint laxity is said to be a predisposing cause in pediatric age group. Atraumatic divergent dislocation of the elbow has been reported in the adults with rheumatoid arthritis. Imaging is challenging because there is no defined specific radiological views, therefore making the diagnosis difficult. This often leads to misdiagnosis or inappropriate treatment. A thorough understanding of mechanism of injury and basis for atypical radiological findings will help in identifying the injury early, and the simple Thompson technique to relocate the elbow will give an excellent functional outcome.

Gene Expression Profiling to Delineate the Anticancer Potential of a New Alkaloid Isopicrinine From Rhazya stricta.

Background:Rhazya stricta has been used as a folkloric medicinal herb for treating various diseases such as diabetes, inflammatory disorders, and sore throat. Several studies have revealed the potential of this plant as an important source of phytochemicals with anticancer properties. Objective: The present study was designed to isolate a novel anticancer compound from Rhazya stricta and elucidate its mechanism of action using genomics approach. Methods:Rhazya stricta leaves extract was prepared, and several alkaloids were purified and characterized. These alkaloids were screened for their anticancer potential. One of the alkaloids, termed as isopicrinine, showed efficient cytotoxicity against MCF7 breast cancer cell line and was selected for further analysis. RNA-Seq transcription profiling was conducted to identify the affected genes and cellular pathways in MCF7 cells after treatment with isopicrinine alkaloid. Results: In vitro studies revealed that newly identified isopicrinine alkaloid possess efficient anticancer activity. Exposure of MCF7 cells with isopicrinine affected the expression of various genes involved in p53 signaling pathway. One of the crucial proapoptotic genes, significantly upregulated in MCF7 after exposure to alkaloid, was PUMA (p53 upregulated modulator of apoptosis), which is involved in p53-dependent and -independent apoptosis. Moreover, exposure of sublethal dose of isopicrinine alkaloid in breast cancer cell line led to the downregulation of survivin, which is involved in negative regulation of apoptosis. Besides, several genes involved in mitosis and cell proliferation were significantly downregulated. Conclusion: In this article, we report the determination of a new alkaloid isopicrinine from the aerial parts of Rhazya stricta with anticancer property. This compound has the potential to be developed as a drug for curing cancer.

Proteomic analysis of naturally occurring boron tolerant plant Gypsophila sphaerocephala L. in response to high boron concentration.

Gypsophila sphaerocephala is a naturally Boron (B) tolerant species that can grow around the B mining areas in Turkey, where the B concentration in soil reaches a lethal dose for plants (up to ∼8900mgkg-1 (∼140mM). While its interesting survival capacity in extremely B containing soils, any molecular research has been conducted to understand its high tolerance mechanism yet. In the present study, we have performed a proteomic analysis of this plant to understand its high tolerance towards B-stress. Seedlings of G. sphaerocephala were collected from B mining area and were adapted to greenhouse conditions. An excessive level of Boric acid (3mM)was applied to the plantlets for 24h. Total proteins were precipitated by using TCA/Acetone method. 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis) analysis of the proteins was carried out. Out of 121 protein spots, 14 were differentially expressed between the control and B-exposed G. sphaerocephala roots. The peptide profile of each protein was determined by MALDI-TOF mass spectrometer after in-gel trypsin digestion. The identified proteins are involved in different mechanisms in the cell such as in antioxidant mechanism, energy metabolism, protein degradation, lipid biosynthesis and signaling pathways, indicating that G. sphaerocephala has multiple cooperating mechanisms to protect itself from high B levels. Overall, this study sheds light on to the possible regulatory switches (gene/s) controlling the B-tolerance proteins and their possible roles in plant's defense mechanism.

Outcomes of Geriatric Hip Fractures Treated with AFFIXUS Hip Fracture Nail.

Geriatric hip fractures are one of the commonest fractures worldwide. The purpose of this study was to report the outcomes of a series of unstable geriatric hip fractures treated with AFFIXUS hip fracture nail. A retrospective study of 100 unstable geriatric hip fractures treated with AFFIXUS hip fracture nail is presented. The mean follow-up duration was 8 months (range 3-32). Of the patients 83% were female. The average age was 85 years. The fracture was treated by closed reduction and intramedullary fixation. The mean acute hospital stay was 17.6 days. Systemic complications occurred in 29 patients (29%) and local complications in 3 patients (3%) including lag screw cutout in one patient (1%), lag screw backout in one patient (1%), and deep infection in one patient (1%). Mechanical failures and periprosthetic fractures were not observed in our series. Fractures united in all patients. Preinjury activity level was recovered in 78% of the patients. The results of AFFIXUS hip fracture nail were satisfactory in most elderly patients. The unique design of the lag screw and its thread spacing had effectively reduced cut-out rate.

Risk factors of mortality among dengue patients admitted to a tertiary care setting in Kerala, India.

Dengue is one of the most serious and rapidly emerging tropical mosquito-borne diseases. The state of Kerala in India is hyperendemic for the disease and is one of the leading states in the reporting of deaths due to dengue. As primary prevention of dengue has had limited success, the prevention of mortality through the identification of risk factors and efficient patient management is of utmost importance. Hence, a record-based case control study was conducted in the Medical College Hospital in Thiruvananthapuram to identify the risk factors of mortality in patients admitted with dengue. Dengue patients over 40years of age were 9.3 times (95% CI; 1.9-44.4) more likely to die compared with younger patients. The clinical features associated with mortality from dengue were altered sensorium (odds ratio (OR) - 156, 95% CI; 12.575-1935.197), abnormal reflexes (OR - 8.5, 95% CI; 1.833-39.421) and edema (OR - 13.22, 95% CI; 2.651-65.951). Mortality was also higher in those patients with co-morbidities such as diabetes mellitus (OR - 26, 95% CI; 2.47-273.674) and hypertension (OR - 44, 95% CI; 6.23-315.499). The independent predictors of mortality were altered sensorium and hypertension. Dengue fever patients with these clinical features and those who are elderly should be more rigorously monitored and promptly referred from lower settings when required to reduce mortality.

Clinical assessment of the shoulder.

The shoulder joint is complex in structure and functionality. It is often difficult to assess clinically due to the great variety of associated pathology. This article presents an overview of the anatomy of the shoulder region and associated pathologies, whilst providing a summary of the clinical examination of the shoulder and associated 'special tests'. A full history is vital when assessing shoulder pathology. No particular test is fully sensitive or specific alone and accuracy varies between both clinicians and patients alike. Assessment of the shoulder should be conducted systematically with a range of tests combined.

Superior labral anterior posterior lesions of the shoulder.

Superior labrum anterior and posterior (SLAP) lesion is of fairly recent description and its understanding is rapidly evolving. Its incidence and need for surgical treatment has increased exponentially in line with the increase in shoulder arthroscopies. It is of particular importance in the elite over head athlete and the young. A range of arthroscopic techniques and devices have been described with good functional results. The ability to return to pre injury level of sports remains a concern.

Reverse shoulder arthroplasty - a literature review.

Professor Grammont revolutionised shoulder surgery with his reverse shoulder arthroplasty design. Patients who had poor results from a conventional shoulder replacement because of cuff deficiency can now be treated effectively. Although designed for cuff tear arthropathy, indications continue to evolve and broaden. The initial results look very promising and the implant has gained much popularity over the years. The article provides an extensive literature review of the indications, results and complications for reverse shoulder arthroplasty.

An overview of shoulder instability and its management.

The assessment and management of patients with instability of the shoulder joint can be challenging, due to the varying ways patients present, the array of different classification systems, the confusing terminology used and the differing potential management strategies. This review article aims to provide a clear explanation of the common concepts in shoulder instability and how they relate to the assessment and management of patients. There are sections covering the mechanisms of shoulder stability, the clinical assessment of patients and imaging techniques. Beyond that there is a discussion on the common classifications systems used and the typical management options. Some patients fall into reasonably well defined categories of classification and in these cases, the management plan is relatively easy to define. Unfortunately, other patients can elude simple classification and in these instances their management requires very careful consideration. Further research may help to facilitate a better understanding of management of the patients in this latter group.

Proximal humeral fractures: a review of current concepts.

The majority of proximal humerus fractures are sustained via low energy falls in the elderly population. These patients can attain an acceptable level of function via non-operative treatment. There is yet to be a clear consensus on treatment options suitable for those that fall outside of this majority group. Open reduction internal fixation, intra medullary nailing and arthroplasty surgery have all been used to varying effects. Good results are achievable if complications such as mal-union, non-union and avascular necrosis can be avoided. This review aims to clarify the options available to the current day trauma surgeon.

Wrist MRI Arthrogram v Wrist Arthroscopy: What are we Finding?

The aim of the study was to compare the radiological findings of wrist arthrogram with wrist arthroscopy. This allowed us to establish the accuracy (sensitivity, specificity) of MRI arthrogram as a diagnostic tool. Thirty patients (20 female and 10 male) have undergone both wrist MRI arthrogram and wrist arthroscopy over the last 3 years at a District General Hospital. The mean age at arthrogram was 42.4 years with an average 6.7 month interval between the two procedures.The MRI arthrogram was reported by a consultant radiologist with an interest in musculoskeletal imaging and the arthroscopies performed by two upper limb surgeons. Patients who underwent both procedures were identified. The arthrogram reports and operation notes were examined for correlation. Three main areas of pathology were consistently examined: TFCC (triangular fibrocartilage complex), scapholunate and lunotriquetral ligament tears. The sensitivity and specificity of arthrogram was calculated for each. Other areas of pathology were also noted.In the case of TFCC tears MRI arthrogram had 90% sensitivity and 75% specificity. The lunotriquetral ligament examination with this technique was 100% sensitivity and specificity. However for scapholunate ligament tears it only had 91% sensitivity and 88% specificity.Wrist arthrogram and arthroscopy are both invasive techniques. In cost terms the arthrogram remains cheaper but is superseded by arthroscopy as it is both diagnostic and therapeutic.

Diagnosis and management of necrotizing fasciitis.

Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue infection which is rapidly fatal unless diagnosed promptly and treated with immediate debridement of necrotic tissue. As early clinical suspicion is paramount to improved survival, this review aims to increase awareness of the condition.