Possible Consequences of Climate Change on Survival, Productivity and Reproductive Performance, and Welfare of Himalayan Yak (Bos grunniens).

Yak are adapted to the extreme cold, low oxygen, and high solar radiation of the Himalaya. Traditionally, they are kept at high altitude pastures during summer, moving lower in the winter. This system is highly susceptible to climate change, which has increased ambient temperatures, altered rainfall patterns and increased the occurrence of natural disasters. Changes in temperature and precipitation reduced the yield and productivity of alpine pastures, principally because the native plant species are being replaced by less useful shrubs and weeds. The impact of climate change on yak is likely to be mediated through heat stress, increased contact with other species, especially domestic cattle, and alterations in feed availability. Yak have a very low temperature humidity index (52 vs. 72 for cattle) and a narrow thermoneutral range (5-13 °C), so climate change has potentially exposed yak to heat stress in summer and winter. Heat stress is likely to affect both reproductive performance and milk production, but we lack the data to quantify such effects. Increased contact with other species, especially domestic cattle, is likely to increase disease risk. This is likely to be exacerbated by other climate-change-associated factors, such as increases in vector-borne disease, because of increases in vector ranges, and overcrowding associated with reduced pasture availability. However, lack of baseline yak disease data means it is difficult to quantify these changes in disease risk and the few papers claiming to have identified such increases do not provide robust evidence of increased diseases. The reduction in feed availability in traditional pastures may be thought to be the most obvious impact of climate change on yak; however, it is clear that such a reduction is not solely due to climate change, with socio-economic factors likely being more important. This review has highlighted the large potential negative impact of climate change on yak, and the lack of data quantifying that impact. More research on the impact of climate change in yak is needed. Attention also needs to be paid to developing mitigating strategies, which may include changes in the traditional system such as providing shelter and supplementary feed and, in marginal areas, increased use of yak-cattle hybrids.

Resolvin D2 promotes host defense in a 2 - hit model of sepsis with secondary lung infection.

In the development of sepsis, there is early, massive inflammation which can lead to multiple organ failure. Later there is an immunosuppressed phase where the host is susceptible to secondary infections or is unable to clear existing infection. Specialized Pro-resolving Mediators (SPMs) are endogenously produced lipids which resolve infection by decreasing bacteria load and reducing systemic inflammatory response. There has been little work studying if SPMs given late, can promote host defense. We examined if an SPM, Resolvin D2 (RvD2) could promote host defense in a 2-hit mouse model of cecal ligation and puncture (CLP) sepsis and secondary Pseudomonas aeruginosa lung infection. RvD2 given 48 h after mild CLP (1st hit), increased gene expression of Toll-like receptor-2 (TLR-2) and alveolar macrophage/monocyte phagocytic ability compared to CLP mice given saline vehicle. In this model, RvD2 did not affect plasma IL-6 or IL-10. These effects induced by RvD2, lowered lung bacterial load and decreased mortality after the secondary infection of Pseudomonas aeruginosa (2nd hit). Splenic T-cell numbers were also increased in RvD2 treated mice compared to saline vehicle treated animals. The results suggest that RvD2 promoted mechanisms of host defense in a 2-hit model sepsis and secondary lung infection.

The Need of Endodontic Therapy among Patients Attending Tertiary Care Center in Central Nepal.

Background Dental caries is considered as the most prevalent oral disease in Nepalese population that frequently needs endodontic therapy or root canal treatment (RCT). Pulp infection is one of the most common sequels of dental caries which when left untreated leads to pulpal necrosis and peri-radicular diseases. Patients usually reports to the dental hospital after there is pain, sensitivity, swelling or fracture of the tooth structure which usually impedes their normal routine of daily life. RCT is one of the efficacious therapeutic procedures that can save the teeth retaining its aesthetics and function. Objective To determine the need of RCT among patients attending Tertiary Care Hospital. Method A cross-sectional epidemiological study was conducted in the Department of Conservative Dentistry and Endodontics over the period of one year from April 2019 to April 2020. Ethical approval was taken from the Institutional Review Committee Kathmandu University School of Medical Sciences. In total, 7566 records of the patients that needed endodontic therapy and other treatments were collected and the need of endodontic therapy versus other treatments were assessed. The data obtained were analyzed using the SPSS version 20. The association between various patient-related variables were calculated by chi square test and mean, standard deviation, frequency and percentage were calculated using descriptive statistics. P value was set at < 0.05 for statistical significance. Result Among the total study population, (n=7566), the mean age was 34.97±14.34 years among which 4387 (58%) were females and 3179 (42%) were males. The type of treatment required by the study participants were significantly associated with age and sex (p < 0.001) and p < 0.001, respectively). Conclusion The findings of this study concluded that there was an increased need for endodontic therapy among patients visiting the department compared to other treatments. There was a significant association between gender and age showing females and elderly patients in greater need for endodontic therapy.

Self-confidence Level among Intern Dentists in Performing Endodontic Treatment Procedures in Nepal.

Background Endodontics is considered as one of the most difficult and stressful disciplines in dentistry. This might be due to the complex anatomical variations, recent advances in equipment, technology, materials and lack of self-confidence. Objective To determine the self-confidence level among the intern dentists in performing endodontic procedures from six different colleges of Kathmandu University, Nepal. Method A descriptive cross-sectional study was conducted among 145 intern dentists. The online questionnaire regarding confidence level (5 point Likert scale) in different endodontic procedures and difficulty level (easy, ok and difficult) with respect to teeth was distributed. For descriptive purpose, frequency and percentage for each response were calculated. Result Dental interns were confident in performing majority of the normal endodontic procedures, however, they showed less confidence in performing difficult steps like rubber dam application for anterior (74, 51%) and posterior tooth (91, 62.7%), use of electronic apex locator (89, 61.4%), using rotary files (114, 78.6%), management of flare-ups (86, 59.4%), assessment of quality of post-endodontic treatment (85, 58.5%), recall periods (75, 51.6%) and performing post and core (82, 56.6%). Likewise, upper first molars (84, 57.9%) and second molars (104, 71.7%) were found to be the most difficult teeth to treat. Conclusion It can be concluded that majority of the dental interns were confident in performing basic endodontic procedures, however, they were found to have low confidence in performing difficult steps. Further training and exposure should be incorporated to increase their confidence level.

Radiographic Assessment of Occurrence of Pulp Stones in Molars of Selected Adult Nepalese Populations at Tertiary Care Center.

Background Pulp stones or "denticles" are a frequent finding in coronal and radicular pulp of primary and permanent dentition. These discrete calcified bodies can be seen in a healthy, diseased and sometimes even in an unerupted tooth. These calcifications are mostly present in molars as free, attached or embedded to dentine of pulp chamber or root canals. Objective To determine the occurrence of pulp stones in molars of selected adult Nepalese population using radiographs and assess the association of its occurrence gender and arch wise. Method A descriptive cross-sectional study was performed using orthopantomogram of total 380 patients (190 male and 190 females) of age group ranging from 16-30 years by convenience sampling. Data were collected through the examination of both hard and soft copies of radiographs under magnification. Pulp stones were scored as present or absent and their association with gender and dental arch were recorded. Descriptive statistics and chi square test was performed to see the prevalence and to compare the occurrence of pulp stone respectively. Result Out of 380 radiographic samples, pulp stones were present in 41.05% of the samples. The occurrence of pulp stones were found to be higher in females than in males, although the difference was not statistically significant (p=0.060).The total number of teeth with pulp stones was 238 and 61 in maxillary and mandibular arches respectively, with statistically significant difference (p<0.001). Conclusion The overall occurrence of pulp stone was found to be 41.05%. It was observed more in females (45.78%) than in males (37%) and more frequently located in maxillary molars (29.2%) than in mandibular molars (8.2%).

Decontaminating N95 and SN95 masks with ultraviolet germicidal irradiation does not impair mask efficacy and safety.

Inadequate supply of filtering facepiece respirators (FFRs) for healthcare workers during a pandemic such as the novel coronavirus outbreak (SARS-CoV-2) is a serious public health issue. The aim of this study was to synthesize existing data on the effectiveness of ultraviolet germicidal irradiation (UVGI) for N95 FFR decontamination. A systematic review (PROSPERO CRD42020176156) was conducted on UVGI in N95 FFRs using Embase, Medline, Global Health, Google Scholar, WHO feed, and MedRxiv. Two reviewers independently determined eligibility and extracted predefined variables. Original research reporting on function, decontamination, or mask fit following UVGI were included. Thirteen studies were identified, comprising 54 UVGI intervention arms and 58 N95 models. FFRs consistently maintained certification standards following UVGI. Aerosol penetration averaged 1.19% (0.70-2.48%) and 1.14% (0.57-2.63%) for control and UVGI arms, respectively. Airflow resistance for the control arms averaged 9.79 mm H2O (7.97-11.70 mm H2O) vs 9.85 mm H2O (8.33-11.44 mm H2O) for UVGI arms. UVGI protocols employing a cumulative dose >20,000 J/m2 resulted in a 2-log reduction in viral load. A >3-log reduction was observed in seven UVGI arms using >40,000 J/m2. Impact of UVGI on fit was evaluated in two studies (16,200; 32,400 J/m2) and no evidence of compromise was found. Our findings suggest that further work in this area (or translation to a clinical setting) should use a cumulative UV-C dose of 40,000 J/m2 or greater, and confirm appropriate mask fit following decontamination.

A Comparative Evaluation of Removal of Intracanal Calcium Hydroxide with Endoactivator System and Mechanical Instrumentation with K File, Using Two Irrigating Solutions: an in Vitro Study.

Background Calcium Hydroxide [Ca(OH)2] is widely used intracanal medicament in endodontics due to its antimicrobial activity against persistent microorganisms. Although routine use of calcium hydroxide is highly recommended, its removal at the time of canal obturation is equally important and challenging because its remnant might prevent the sealer penetration into dentinal tubules, potentially interact with zinc oxide eugenol sealers making them brittle and granular, and adversely affect the bonding of resin sealer adhesion thus significantly increasing the apical leakage of root canal treated teeth. Removal of intracanal calcium hydroxide is performed usually with different irrigants in combinations with ultrasonic, sonic, hand or rotary instruments. Objective The objective of this study is to evaluate the efficacy of Endoactivator system and mechanical instrumentation with K files using two irrigants for removal of intracanal Ca(OH)2. Method Forty extracted single rooted human mandibular premolars were collected and divided into two groups of 20 samples each (N=40; Group A: 1-20; Group B: 21-40). All samples were decoronated, instrumented, irrigated, dried and filled with Ca(OH)2 paste. Samples were stored in a humidor for a week and were instrumented with conventional k-file (Group A) and Endoactivator system (Group B). A radiograph was taken to evaluate the remnants of intracanal medicament. Result Overall there is not any statistically significant difference on any method of intracanal calcium hydroxide removal (p=0.45). However, on section wise comparison of efficacy of Ca(OH)2 removal, Endoactivator seems to be more effective than hand files on apical section (p=0.047). There is no statistically significant difference on coronal and middle segments between two methods (p=0.99). Conclusion The efficacy of removal of calcium hydroxide medicament from overall canal by conventional method and endoactivator system is similar though endoactivator system seems to be relatively more efficient on apical portion of root.

Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis.

BACKGROUND: Infections are associated with biological therapies in psoriasis. OBJECTIVES: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody. METHODS: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. RESULTS: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. CONCLUSIONS: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.

Perioperative management of two cases of hemophilia with spontaneous intracerebral hemorrhage undergoing emergency craniotomy in resource constrained setup of Nepal.

Patients with hemophilia are prone to develop spontaneous intracranial hemorrhage. It carries a significant risk of morbidity and mortality. In this case series, we report two cases of hemophilia who suffered spontaneous intracerebral hemorrhage with features of raised intracranial pressure and were successfully managed perioperatively. The patients were managed with early intensive care unit management, measures to reduce intracranial pressure, perioperative clotting factor administration, airway management and surgery to decrease the raised intracranial pressure. Both patients improved following surgery and were discharged home. Perioperative multidisciplinary management of hemophilia is discussed in this series.

Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. METHODS: To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. RESULTS: Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% (p < 0.05) with RYGB, whereas the effect of insulin on HGP was completely absent in VMH IR knockdown (IRkd) rats. By contrast, both RYGB groups displayed an identical twofold increase in insulin-stimulated peripheral glucose uptake. The animals that underwent control gastrointestinal surgery failed to show any improvement in either hepatic or peripheral insulin sensitivity; VMH IRkd did not influence the magnitude of insulin resistance. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that RYGB surgery in high-fat-fed obese rats enhances hepatic and peripheral insulin sensitivity independently of weight loss. The improved hepatic, but not the peripheral, response to insulin is mediated centrally at the level of the VMH. These data provide direct evidence that the metabolic benefits of RYGB surgery are not simply a consequence of weight loss but likely in part involve the central nervous system.

Improvement in corneal scarring following bacterial keratitis.

AIM: Bacterial keratitis results in corneal scarring and subsequent visual impairment. The long-term evolution of corneal scars has not been well described. In this case series, we identified patients who had improvement in corneal scarring and visual acuity from a clinical trial for bacterial keratitis. METHODS: We searched the records of the Steroids for Corneal Ulcers Trial (SCUT) for patients who had improvement in vision between the 3-month and 12-month visits and reviewed their clinical photographs. RESULTS: Of the 500 patients enrolled in SCUT, five patients with large central corneal scars due to bacterial keratitis are presented. All experienced improvement in rigid contact lens-corrected visual acuity from months 3 to 12. All patients also had marked improvement in corneal opacity during the same time period. None of the patients opted to have penetrating keratoplasty. CONCLUSIONS: Corneal scars may continue to improve even many months after a bacterial corneal ulcer has healed. The corneal remodeling can be accompanied by considerable improvement in visual acuity, such that corneal transplantation may not be necessary.

Endodontic management of radix paramolaris with six canals: a clinical case report.

Endodontic therapy of mandibular molars is a challenging task due to its varied root canal morphology. A mandibular first molar with additional buccal root (Radix paramolaris) and additional distolingual root (Radix Entomolaris) is an example of its varied anatomy. A successful management of atypical root canal configurations is an important aspect in determining the success rate of root canal therapy. The detail knowledge of the root morphology and canal anatomy allows the clinician for accurate location of the extra roots and canals and accordingly the refinement of the access cavity for the stress free entry of complex anatomy. Hence, for a successful root canal therapy, clinician must be aware of the external and internal anatomic variations .The aim of this clinical case report is to present and describe the unusual presence of two separate mesial roots and six root canals in mandibular first molar, detected during routine endodontic therapy.

Predictors of outcome in fungal keratitis.

PURPOSE: To analyse predictors of clinical outcome in fungal keratitis. METHODS: Data was collected during a prospective, randomized, controlled, double-masked clinical trial of treatment for fungal keratitis. Clinical features at presentation and demographics were collected at the enrollment visit for all patients. Pre-specified clinical outcomes included 3-month visual acuity and infiltrate/scar size, time to re-epithelialization, and corneal perforation. A separate multivariable model with each outcome as the dependent variable included all predictor variables. RESULTS: Predictors for worse 3-month visual acuity include older age (P=0.024), worse presentation visual acuity (P<0.001), larger infiltrate size at presentation (P<0.001), and pigmented ulcer (P=0.030). Larger infiltrate size at presentation was a significant predictor of worse 3-month infiltrate/scar size (P<0.001). Larger epithelial defect size was a significant predictor of perforation (P=0.0013). Predictors of longer time to re-epithelialization include infiltrate size at presentation (P<0.001) and older age (P=0.025). CONCLUSION: Ulcer severity at presentation is highly predictive of worse outcomes. Presentation of clinical characteristics such as baseline acuity and infiltrate scar can provide important information to clinicians about prognosis, and may help guide management and treatment decisions. Prevention of corneal ulcer remains important, as it is difficult to change the course of the ulcer once it has begun.

Co-trimoxazole-induced myopia in an HIV-positive patient.

Co-trimoxazole is a commonly used drug in the treatment and prophylaxis of opportunistic infections in HIV seropositive patients. We report a case of a 35-year-old HIV-infected man who presented with blurring of vision one week following initiation of co-trimoxazole therapy. A diagnosis of co-trimoxazole-induced myopia, a known idiosyncratic drug reaction, was made. The drug was withheld and the myopia resolved completely. Although in this patient the ocular condition resolved completely, serious ocular adverse reactions have also been reported with co-trimoxazole. This case report highlights the occurrence of ocular adverse drug reactions (ADRs) in HIV-infected patients on co-trimoxazole and the complexity of drug interactions.

Antioxidant and hepatoprotective action of Asparagus racemosus Willd. root extracts.

The antioxidant activities of the crude hydro-alcoholic extract (CE) and its four fractions viz. methanol (MF), ethyl acetate (EF), n-Butanol (BF), and precipitated aqueous (PAF) of A.racemosus roots tested decreased in the order of EF > MF > CE > BF > PAF when investigated by DPPH free radical scavenging assay. Under iron induced lipid peroxidation almost similar results were observed except that the activity was more in PAF than BF. Hepatoprotective activity of the extracts was also demonstrable in vivo by the inhibition of-CCl4 induced formation of lipid peroxides in the liver of rats by pretreatment with the extracts. CCl4-induced hepatotoxicity in rats, as judged by the raised serum enzymes viz. glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase and total and direct bilirubin as well as oxidant enzyme viz. malon dialdehyde were prevented, while antioxidant enzymes viz. superoxide dismutase, reduced glutathione and catalase were elevated by pretreatment with the extracts, demonstrating the potent hepatoprotective action of the roots of A. racemosus.

Early diagnosis of typhoid fever by nested PCR for flagellin gene of Salmonella enterica serotype Typhi.

BACKGROUND & OBJECTIVES: Typhoid fever caused by Salmonella Typhi continues to be a major health problem in spite of the use of antibiotics and the development of newer antibacterial drugs. Inability to make an early laboratory diagnosis and resort to empirical therapy, often lead to increased morbidity and mortality in cases of typhoid fever. This study was aimed to optimize a nested PCR for early diagnosis of typhoid fever and using it as a diagnostic tool in culture negative cases of suspected typhoid fever. METHODS: Eighty patients with clinical diagnosis of typhoid fever and 40 controls were included in the study. The blood samples collected were subjected to culture, Widal and nested PCR targeting the flagellin gene of S. Typhi. RESULTS: The sensitivity of PCR on blood was found to be 100 per cent whereas the specificity was 76.9 per cent. The positive predictive value (PPV) of PCR was calculated to be 76.9 per cent with an accuracy of 86 per cent. None of the 40 control samples gave a positive PCR. INTERPRETATION & CONCLUSIONS: Due to its high sensitivity and specificity nested PCR can be used as a useful tool to diagnose clinically suspected, culture negative cases of typhoid fever.

Antibiotic resistance pattern among common bacterial uropathogens with a special reference to ciprofloxacin resistant Escherichia coli.

BACKGROUND & OBJECTIVES: The resistance of bacteria causing urinary tract infection (UTI) to commonly prescribed antibiotics is increasing both in developing as well as in developed countries. Resistance has emerged even to more potent antimicrobial agents. The present study was undertaken to report the current antibiotic resistance pattern among common bacterial uropathogens isolated in a tertiary care hospital in south India, with a special reference to ciprofloxacin. METHODS: A total of 19,050 consecutive urine samples were cultured and pathogens isolated were identified by standard methods. Antibiotic susceptibility was done by Kirby Bauer disk diffusion method. The clinical and demographic profile of the patients was noted. RESULTS: Of the 19,050 samples, 62 per cent were sterile, 26.01 per cent showed significant growth, 2.3 per cent showed insignificant growth and 9.6 per cent were found contaminated. Significant association (P<0.001) of prior use of antibiotics in males, UTI in adults, gynaecological surgery in females, obstructive uropathy in males and complicated UTI in females with the occurrence of UTI with ciprofloxacin resistant Escherichia coli was noted. Significant association was noted in females with prior antibiotics, with prior urological surgery and in males with prior complicated UTI. There was no significant association with diabetes mellitus with the occurrence of UTI with ciprofloxacin resistant E. coli. Fluoroquinolone resistance was found to increase with age. INTERPRETATIONS & CONCLUSIONS: Ciprofloxacin resistance has emerged due to its frequent use. This resistance was seen more in the in-patients, elderly males and females. Also the resistance to other antibiotics was also high. Increasing antibiotic resistance trends indicate that it is imperative to rationalize the use of antimicrobials in the community and also use these conservatively.

Microbiological cure times in acanthamoeba keratitis.

AIMS: The purpose of this study was to estimate the duration of treatment necessary for sequential acanthamoeba laboratory tests from corneal scrapings to become negative, and to assess predictors that affect this duration period. METHODS: We included all patients with at least one positive acanthamoeba culture or Giemsa stain at the F.I. Proctor Foundation Microbiology Laboratory from 1996 to 2009. A parametric survival analysis was performed among patients with repeat cultures to assess significant predictors for extended clearance time. Simulations were performed to estimate clearance time in the entire patient population, assuming imperfect sensitivity. RESULTS: Thirty-seven patients with laboratory evidence of acanthamoeba had testing at 69 time points. The median clearance time among eyes with repeat cultures was 42.5 days (interquartile range (IQR) 22.0-82.0 days; unadjusted parametric model). Initial visual acuity was the only predictor significantly associated with clearance time in univariate analyses (P<0.0001). Using initial visual acuity as a predictor for clearance time among the entire patient population, the estimated clearance time decreased to 38.7 days (95% confidence interval (CI) 27.9-53.5 days). When the imperfect sensitivity of the culture technique was also taken into account, the estimated clearance time was 44.1 days (95% CI 31.9-61.0 days). CONCLUSION: The duration of infection with acanthamoeba keratitis undergoing treatment has not been well characterized. In this report we estimate a median clearance time of approximately 6 weeks, with an IQR of 22-82 days.

Hemophagocytic syndrome in a child with brucellosis.

The authors report case of a two and half years old female child presented with fever for one month with hepatosplenomegaly. Though the child had been symptomatic for a prolonged period, she did not appear very unwell at presentation. However, after admission there was sudden rapid deterioration of her clinical status. Investigations revealed hemophagocytosis with brucella infection.