UNDERSTANDING THE ADAPTATION AND SENSITIVITY OF THE MICROBIOME: MICROBIAL RESILIENT AND HUMAN WELL-BEING.

The term microbiome describes the assortment of microbes that dwell in and on a person's body, particularly in the gut, comprising fungi, bacteria, infectious agents and additional microbes. According to research, numerous elements of human well-being, such as digestion, immunological response and psychological well-being, have been linked to the microbiome. Preserving human wellness requires knowledge of the microbiome's stability and how it reacts to perturbations. According to preliminary research, adults' microbial ecosystems are considered stable with no signs of significant disturbances. This stability is not preserved by inertia and the system's interaction with restorative forces keeps the processes stable. Short antibiotic doses can result in quick and substantial microbiome alterations. However, there is confirmation that the taxonomic structure of the microbiome has at least recovered after such disruptions. The effect of antibiotics is individualized and can be altered by earlier exposure to a similar drug, which is a crucial aspect to remember. These results suggest that the individual's microbiome has adaptable qualities. Examining the microbiome's reactions to perturbations might be helpful in the prediction of potential instabilities and illness by revealing important features of function, microbial connections, and important species in the native microbiota. This information can benefit the management of the individual microbial community and the promotion of better health conditions.

INNOVATIONS IN FOCUS: MECHANISTIC DISEASE THEORIES, CLIMATE DYNAMICS, AND HOST-PARASITE ADAPTATIONS.

Infectious illnesses are predicted to experience a range of intricate responses from climate change, with some likely to rise, others to fall and many expected to undergo changes in prevalence. The study uses extensive data on global temperature variations and infectious illness transmission in people and animals. We now know a lot more about how the temperature changes across the world and whether or not the spread of infectious diseases impacts people as well as animals. Three primary topics of research are investigated in this paper: improving mechanical disease modelling, investigating the role of environmental variation in sickness dynamics, and understanding the consequences of temperature imbalances between parasites and hosts. By incorporating the latest data stemming from these advancements into weather-disease models and bridging critical knowledge gaps, enhancing our ability to forecast the probable effect of rising temperatures on the prevalence of diseases among both human and animal communities is possible. Through the establishment of important information gaps and the incorporation of new findings into models of climate-disease relationships, it will be possible to predict the effects of changes in climatic averages, variations and extremes on people and wildlife health.

UNDERSTANDING THE LONG-TERM INTERPLAY BETWEEN GLUCOCORTICOIDS, PARATHYROID HORMONE LEVELS, AND OSTEOPOROSIS IN PATIENTS.

Drugs called glucocorticoids (GC) are often prescribed for both inpatient and outpatient settings. They are often used to treat a number of disorders due to their anti-inflammatory activity. Long-term use of GCs, especially long-term high-dose administrations, may result in a variety of negative effects. In Hilla City, Babylon Governorate of Iraq, Merjan Teaching Hospital, Al-Hilla Teaching Hospital's Joint Enology Clinic, and Al-Imam Al-Sadiq Hospital, were the sites of this case-control research, which was carried out. There were 100 total participants in this trial, of whom 50 were patients with osteoporosis (OP). The ages of the patients and the control collection were. They were chosen since their gender and ages matched. The findings show extensively senior level of parathyroid hormone (PTH) in OP patients when compared to the control group, whereas calcium (Ca) level into the patient group significantly lowered during association toward the manage set. In summary, there is a positive correlation between PTH and the condition of bone mineralization. In those who use GCs for a long time, PTH may be used as a prognostic marker to predict when bone mineral abnormalities would develop.

AMR Sign - An Arthroscopic S-shaped Fold Signifying Adequate Medial Meniscus Repair.

Introduction: The preferred management of medial meniscus tears has notably moved from meniscectomies towards repair. With a higher volume of meniscal repairs being done all across the world with every passing day, the lack of an objective and definitive sign suggesting the adequacy of its repair is daunting. The purpose of our study was to introduce a unique and novel arthroscopic sign formed after adequate repair of the medial meniscus, the AMR (Adequacy of Medial meniscus Repair) sign. We hypothesised that it is not only the objective end point for repair, but can also form the indicator for excellent clinical, functional, and radiological outcome even in the long term. Materials and methods: This was a multicentric, prospective study initiated by the corresponding author, and the findings validated subsequently by the other authors. Overall, it included 804 patients of isolated medial meniscus tear operated with arthroscopic all-inside technique between January 2014 and December 2017. Patients were segregated into three groups based on whether an S-shaped curve in the free, inner edge of the medial meniscus sign was formed post-repair, lost after further tightening, or not formed upon subjective completion of repair. All the patients were followed-up and evaluated based of medial joint line tenderness, McMurray's test for medial meniscus, IKDC score, WOMET score, and radiologically using an MRI at the terminal follow-up. Results: The mean terminal follow-up was 42.34±4.54 months. There was significant (p<0.01) improvement in all patients at the terminal follow-up post-surgery, irrespective of the group. The group in which AMR sign was formed and maintained showed a significantly better functional outcome on terminal follow-up as well as lower failure rates compared to the other two groups. Conclusion: AMR sign is an S-shaped fold at the inner, free edge of medial meniscus, formed after an adequate repair of isolated medial meniscus tear, as viewed on arthroscopy. It is an objective sign denoting regained integrity of the collagen architecture of the medial meniscus following repair. It is also a reliable indicator of excellent long term functional, clinical, and radiological outcome and also lower failure rates in patients after arthroscopic medial meniscus repair.

THE IMPACT OF SLEEP ON PHYSICAL AND MENTAL HEALTH: IMPORTANCE OF HEALTHY SLEEP HABITS.

Sleep is an important part of health, and when you go to sleep, how long you sleep, and how well you sleep all have a big impact on your health. Sleep may be required for regulating the body's metabolism, feelings, function, memory storage, brain recovery, and learning. Because of how important these processes are, sleep should be seen as just as important to health as what you eat and how much you exercise. Adults' sleep generally gets shorter and less restful, their sleep starts later and is more broken up, they have more sleep problems, and their rest-activity rhythms get weaker. In addition to receiving enough sleep (quality), healthy sleep habits also include maintaining a consistent sleep schedule. Ninety male college students with varying sleep schedules were analyzed for their physical and emotional well-being. By using factor analysis to categorize individuals' sleeping patterns across three dimensions regularity, quality, and quantity. We were able to develop sleep-habit measures. Clustering identified four distinct patterns of sleep behavior: good sleep was defined by regular, high-quality sleep despite being of comparatively brief duration; long sleep was predictable, fairly lengthy, but of minimal quality; short sleep was of excellent quality despite being short and irregular; and poor sleep was erratic, low-quality, and relatively long. The excellent sleepers also had reduced diastolic and systolic and a smaller means waist measurement. In addition, the poor sleepers had the lowest average MCS scores of all of the study groups. Poor sleepers also had the lowest mean scores on the Subjective Depression Scale (SDS). Issues involving glucose or lipid absorption were also more common in the short-term and long poor-sleep categories. Without restful sleep and a regular bedtime routine, it is impossible to maintain excellent mental and physical wellness, even if time and sleep are maintained constantly. Therefore, to produce suitable sleep recommendations for enhanced mental and physical health, we evaluated not only the quantity of sleep but also its consistency and high quality.

Listeria Meningitis, one of your five a day? A case report of Listeria Monocytogenes Meningitis in a fit and well 62-year-old woman.

Listeria Monocytogenes is transmitted via ingestion of contaminated food products and can cause invasive disease in susceptible hosts. Risk factors include immunocompromise; pregnancy; being elderly; and new-born. Listeriosis is uncommon but can occur in immunocompetent individuals and has a high mortality rate. We report a case of a 62-year-old female with no obvious risk factors who presented with atypical meningism. The patient was subsequently diagnosed with listeria meningitis and made a good recovery. The patient was a gardener regularly handling soil and ingested vegetables from her allotment patch; this case is reported to highlight less common risk factors and atypical ways in which listeria may present to the acute medical take.

Perineural and intravenous dexamethasone and dexmedetomidine: network meta-analysis of adjunctive effects on supraclavicular brachial plexus block.

Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the effects of dexamethasone and dexmedetomidine based on their administration routes have not been directly compared, and the relative extent to which each adjunct prolongs sensory blockade remains unclear. This network meta-analysis sought to compare and rank the effects of perineural and intravenous dexamethasone and dexmedetomidine as supraclavicular block adjuncts. We sought randomised trials investigating the effects of adding perineural and intravenous dexamethasone or dexmedetomidine to long-acting local anaesthetics on supraclavicular block characteristics, including time to block onset and durations of sensory, motor and analgesic blockade. Data were compared and ranked according to relative effectiveness for each outcome. Our primary outcome was sensory block duration, with a 2-h difference considered clinically important. We performed a frequentist analysis, using the GRADE framework to appraise evidence. One-hundred trials (5728 patients) were included. Expressed as mean (95%CI), the control group (local anaesthetic alone) had a duration of sensory block of 401 (366-435) min, motor block duration of 369 (330-408) min and analgesic duration of 435 (386-483) min. Compared with control, sensory block was prolonged most by intravenous dexamethasone [mean difference (95%CI) 477 (160-795) min], followed by perineural dexamethasone [411 (343-480) min] and perineural dexmedetomidine [284 (235-333) min]. Motor block was prolonged most by perineural dexamethasone [mean difference (95%CI) 294 (236-352) min], followed by intravenous dexamethasone [289 (129-448)min] and perineural dexmedetomidine [258 (212-304)min]. Analgesic duration was prolonged most by perineural dexamethasone [mean difference (95%CI) 518 (448-589) min], followed by intravenous dexamethasone [478 (277-679) min] and perineural dexmedetomidine [318 (266-371) min]. Intravenous dexmedetomidine did not prolong sensory, motor or analgesic block durations. No major network inconsistencies were found. The quality of evidence for intravenous dexamethasone, perineural dexamethasone and perineural dexmedetomidine for prolongation of supraclavicular sensory block duration was 'low', 'very low' and 'low', respectively. Regardless of route, dexamethasone as an adjunct prolonged the durations of sensory and analgesic blockade to a greater extent than dexmedetomidine. Differences in block characteristics between perineural and intravenous dexamethasone were not clinically important. Intravenous dexmedetomidine did not affect block characteristics.

Investigating the appropriateness of physician-ordered diagnostic computed tomography for patient management in a rural hospital in New South Wales, Australia.

AIM: To examine the performance of "appropriate" versus "inappropriate" computed tomography (CT) and to examine whether physicians who practise in a rural hospital in NSW Australia, achieved imaging appropriateness in their ordering of diagnostic CT examinations. MATERIALS AND METHODS: An audit of the electronic medical records of medical ward inpatients (during the 2016/2017 financial year) was carried out. De-identified data were extracted for all patients who had undergone diagnostic CT while on admission. Using the SPSS analytical software, chi-square tests for independence were conducted to check for difference between appropriate and inappropriate CT imaging. RESULTS: Of all the CT procedures, 92% were found to be appropriate. Appropriate CT confirmed the provisional diagnosis in more instances than inappropriate CT (132 versus three). This observed difference was significant with a small size effect (chi-squared [1, n=362]=8.58, p=0.003, φ=0.16). Similarly, appropriate CT significantly facilitated a change in the proposed direction of care (140 versus 40) (chi-squared [1, n=362]=7.75, p=0.005, φ=0.16). In addition, appropriate CT which confirmed diagnosis, resulted in a change in the proposed direction of care as opposed to inappropriate CT (115 versus one; chi-squared [1, n=362]=8.11, p=0.004, Cramer's V=0.24). CONCLUSION: Specialist physicians who practise in a rural hospital setting achieved CT appropriateness. Appropriate CT is beneficial to patient care. Adhering to recommended imaging guidelines is essential for achieving imaging appropriateness.

High intensity focused ultrasound: The fundamentals, clinical applications and research trends.

Diagnostic ultrasound has been clinically used for decades. More recently, high intensity focused ultrasound (HIFU) has been developed for therapeutic use as a non-invasive technique for tissue ablation. HIFU is also being investigated for advanced applications at the cellular level. Under guidance by magnetic resonance or ultrasound imaging, HIFU can achieve precise biological effects in tissue with a high safety profile. In this article, we discuss the basic principles, advantages and limitations of HIFU. We will also address the food and drug administration (FDA) approved clinical applications in the United States and highlight active HIFU research with promising clinical outcomes.

Use of epidural clonidine for the management of analgesia in the opioid addicted parturient on buprenorphine maintenance therapy: an observational study.

OBJECTIVES: Management of labor analgesia and post-cesarean delivery pain is challenging in the patient taking buprenorphine as opioid addiction maintenance therapy. We observed whether substituting clonidine for fentanyl in an epidural solution would provide adequate analgesia for labor and after cesarean delivery. METHODS: We substituted our standard 2 µg/mL fentanyl in 0.0625% bupivacaine epidural solution with 2 µg/mL clonidine in 0.0625% bupivacaine, or 1.2 µg/mL clonidine in 0.1% bupivacaine, for labor and post-cesarean analgesia in parturients on buprenorphine therapy. All cesarean deliveries were performed with a combined spinal-epidural technique and the catheters maintained for immediate postoperative analgesia using an epidural infusion. Catheters were discontinued the next day and patients were then managed with other analgesics based on obstetric preference. We recorded pain scores during labor and in the immediate post-surgical period; and supplemental medications given after epidural catheter removal. RESULTS: Fourteen patients were included in the study, of whom seven presented in spontaneous labor and seven had elective cesarean delivery. All laboring patients achieved good analgesia, and five of seven avoided supplemental opioid use in the postpartum phase. Of the postsurgical patients, six of seven had pain scores less than 5/10 at epidural catheter removal and three of seven avoided supplemental opioids postoperatively. CONCLUSIONS: The combination of clonidine and bupivacaine appears effective in parturients on buprenorphine therapy for opioid addiction maintenance. As study numbers were small and several factors were not examined, further confirmatory research is needed, including to determine the ideal dose of epidural clonidine in this setting.

Systemic lupus erythematosus is not a risk factor for poor outcomes after total hip and total knee arthroplasty.

OBJECTIVES: Historically, arthroplasty in systemic lupus erythematosus (SLE) patients has been less successful than for patients with osteoarthritis (OA). It is not known if SLE remains an independent risk factor for poor arthroplasty outcomes or if other factors, such as avascular necrosis (AVN), continue to play a role. METHODS: A case-control study using data from a single-institution arthroplasty registry compared SLE total hip arthroplasty (THA) and total knee arthroplasty (TKA) with OA controls matched by age, gender and presence of AVN. Baseline, two-year administrative and self-report data, and diagnosis leading to arthroplasty were evaluated. RESULTS: A total of 54 primary SLE THA and 45 primary SLE TKA were identified from May 2007 through June 2011. AVN was present in 32% of SLE THA and no TKA. SLE THA had worse preoperative WOMAC pain (42.5 vs. 52.7; p = 0.01) and function (38.8 vs. 48.0; p = 0.05) compared with OA. However, at two years there was no difference in WOMAC pain (91.1 vs. 92.1; p = 0.77) or WOMAC function (86.4 vs. 90.8; p = 0.28). SLE TKA were similar to OA in both preoperative pain (42.6 vs. 48.4; p = 0.14) and function (42.1 vs. 46.8; p = 0.30) and two-year pain (85.7 vs. 88.6; p = 0.50) and function (83.7 vs. 85.1; p = 0.23). Compared to OA, SLE THA and TKA patients had more renal failure (14% vs. 1%; p = 0.007) and hypertension (52% vs. 29%; p = 0.009). In a multivariate linear regression, SLE was not predictive of either poor pain or poor function. CONCLUSIONS: While SLE patients have more comorbidities than OA, and SLE THA have worse preoperative pain and function compared with OA controls, SLE was not an independent risk factor for poor short-term pain or function after either hip or knee arthroplasty.

Development and Validation of Stability-indicating RP-HPLC Method for Estimation of Pamabrom in Tablets.

The present study depicts the development of a validated RP-HPLC method for the determination of the pamabrom in presence of degradation products or other pharmaceutical excipients. Stress study was performed on pamabrom and it was found that it degrade sufficiently in acidic, alkali and oxidative condition but less degradation was found in thermal and photolytic condition. The separation was carried out on Enable G 120 A(0) (250×4.6 mm, 5 µ) column having particle size 5 µ using methanol: water (75:25 v/v) with pH 4.0 adjusted with ortho phosphoric acid as mobile phase at flow rate of 1 ml/min. The wavelength of the detection was 280nm. A retention time (Rt) nearly 3.9 min was observed. The calibration curve for pamabrom was linear (r (2) = 0.9997) from range of 10-60 µg/ml with limit of detection and limit of quantification of 1.41 µg/ml and 4.28 µg/ml, respectively. Analytical validation parameter such as selectivity, specificity, linearity, accuracy and precision were evaluated and relative standard deviation value for all the key parameters were less than 2.0%. The recovery of the drug after standard addition was found to be 101.35%. Thus, the developed RP-HPLC method was found to be suitable for the determination of pamabrom in bulk as well as stability samples of tablets containing various excipients.

Risk assessment of neonatal excipient exposure: lessons from food safety and other areas.

Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates without obvious adverse effects. Some excipients may be toxic in high amounts in which case they need careful risk assessment. Alternatively, it is conceivable that ill-founded fears about excipients mean that potentially useful medicines are not made available to newborn babies. Choices about excipient exposure can occur at several stages throughout the lifecycle of a medicine, from product development through to clinical use. Making these choices requires a scalable approach to analysing the overall risk. In this contribution we examine these issues.

A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women.

Irisin, a newly discovered, PGC-1α dependent myokine, has recently been shown to increase in circulation in response to sprint exercise. This study examined the effect of prolonged exercise on irisin concentrations in young men (n=7) as well as in young women (n=5) during different stages of the menstrual cycle. Seven young men completed 90 min of treadmill exercise at 60% of VO2max and a resting control trial. Five women completed the same exercise protocol in two different trials: during the early follicular phase and mid-luteal phase of the menstrual cycle. Blood samples were collected and analyzed for irisin concentrations immediately before exercise, at 54 and 90 min of exercise, and at 20 min of recovery (R20). Findings revealed that by 54 min of a 90 min treadmill exercise protocol at 60% of VO2max, irisin concentrations significantly increased 20.4% in young men and 20.3% as well as 24.6% in young women during the early follicular and mid-luteal phases of the menstrual cycle, respectively. However, by 90 min of exercise as well as R20, irisin concentrations were no longer elevated. Stage of the menstrual cycle did not affect responses in young women. Findings indicate that prolonged aerobic exercise produces a transient increase in irisin concentrations during the first hour of exercise for both genders and suggest that this form of moderate exercise may be helpful in improving fat metabolism.

An update on the genetics of pheochromocytoma.

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors. About 30% or more of them are thought to be of inherited origin due to germ-line mutations in at least 10 well-characterized genes. There are data linking specific genotypes of these tumors to specific locations, typical biochemical phenotypes or future clinical behaviors. Conversely, clinical features, catecholamine production and immunohistochemistry evaluation can help with the proper order of genetic testing for PHEO and PGL. The identification of a germ-line mutation can lead to an early diagnosis, appropriate treatment, regular surveillance and better prognosis not only for the patient but also for their family members. Moreover, the latest discoveries in molecular pathogenesis of these tumors will provide an important basis for future personalized therapy.

Characterizing cognitive deficits and dementia in an aging urban population in India.

Rapid rise in the population of older adults in India will lead to the need for increased health care services related to diagnosis, management, and long-term care for those with dementia and cognitive impairment. A direct approach for service provision through memory clinics can be an effective, successful, and sustaining means of delivering specialized health care services. We have established a memory clinic in Mumbai, India by employing the diverse clinical skills available in Indian academic institutions, diagnostic and research expertise of clinicians and psychologists, and the support of the U.S. National Institutes of Health. Our project involved recruitment of patients, clinical and neuropsychological assessment, and standardized diagnostic procedures, demonstrating the feasibility of using research methods to develop a memory clinic. In this paper, we describe the development of a community-based memory clinic in urban India, including linguistic and cultural factors and present detailed results, including diagnostic characterization, on 194 subjects with various stages of cognitive deficits. Our findings support the feasibility of developing a memory clinic in a public hospital and successful use of research diagnostic criteria to categorize cognitive deficits observed in this population, which may be used to inform the development of other such clinics.

Pheochromocytoma: implications in tumorigenesis and the actual management.

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.

Improved cellulase production by Botryosphaeria rhodina from OPEFB at low level moisture condition through statistical optimization.

The response surface method was applied in this study to improve cellulase production from oil palm empty fruit bunch (OPEFB) by Botryosphaeria rhodina. An experimental design based on a two-level factorial was employed to screen the significant environmental factors for cellulase production. The locally isolated fungus Botryosphaeria rhodina was cultivated on OPEFB under solid-state fermentation (SSF). From the analysis of variance (ANOVA), the initial moisture content, amount of substrate, and initial pH of nutrient supplied in the SSF system significantly influenced cellulase production. Then the optimization of the variables was done using the response surface method according to central composite design (CCD). Botryosphaeria rhodina exhibited its best performance with a high predicted value of FPase enzyme production (17.95 U/g) when the initial moisture content was at 24.32%, initial pH of nutrient was 5.96, and 3.98 g of substrate was present. The statistical optimization from actual experiment resulted in a significant increment of FPase production from 3.26 to 17.91 U/g (5.49-fold). High cellulase production at low moisture content is a very rare condition for fungi cultured in solid-state fermentation.