Effect of prostaglandin alone and in combination with trace minerals on the follicular and luteal dynamics, estrus response and pregnancy in sub-estrus buffaloes (Bubalus bubalis).

Sub-estrus is a condition when buffaloes do not display behavioural estrus signs, despite being in estrus and causes a delay in conception and increases the service period. The present study describes the effect of synthetic prostaglandin (PGF2α) alone and in combination with trace minerals on the follicular and corpus luteum (CL) dynamics, serum estradiol (E2) and progesterone (P4) concentration correlating estrus response and pregnancy outcome in sub-estrus buffaloes during the breeding season. A total of 50 sub-estrus buffaloes, identified through ultrasonography (USG) examination, were randomly allocated into three groups, viz. T1 (Synthetic PGF2α, Inj. Cloprostenol 500 µg, i.m, n = 17), T2 (Synthetic PGF2α + Trace mineral supplementation, Inj. Stimvet 1 mL/100 kg body weight, i.m., n = 17) and control (untreated; n = 16). Following treatment, 100% of sub-estrus buffaloes were induced estrus in the T1 and T2 groups, while only 18.75% were induced in the control. The CL diameter and serum P4 concentration were significantly lower at post-treatment, whereas the pre-ovulatory follicle (POF) size and serum E2 concentration were significantly higher in the T1 and T2 groups as compared to the control (p < .05). The buffaloes of the T2 group had a greater proportion of moderate intensities estrus than those of T1. Moreover, the proportion of buffaloes conceived in the T1 and T2 were 41.2% and 52.95%, respectively. The larger POF diameter and higher serum E2 concentration were associated with intense intensity estrus and higher conception rate (66.7%) in sub-estrus buffaloes. Similarly, CL regression rate, POF size and serum E2 concentration were relatively higher in the buffaloes conceived as compared to those not conceived. It is concluded that synthetic PGF2α in combination with trace minerals induces moderate to intense intensities estrus in a greater proportion of sub-estrus buffaloes and increases the conception rate during the breeding season. Moreover, behavioural estrus attributes correlating follicle and luteal morphometry, serum E2 and P4 concentration could be used to optimise the breeding time for augmenting the conception rate in sub-estrus buffaloes.

Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

Successful autotransplantation of a mature mesiodens to replace a traumatized maxillary central incisor.

AIM: This case describes the successful transplantation of a mature mesiodens tooth to replace a traumatized maxillary central incisor. SUMMARY: A 17-year-old male attended 1 week after a traumatic injury to his left maxillary central incisor (tooth 21). Radiographs revealed a horizontal root fracture and a poor prognosis. The tooth was atraumatically removed and replaced with a mesiodens lying in the same region. After stabilization, root canal treatment was performed and aesthetics were restored with a tooth coloured restoration. A 2-year follow-up revealed the tooth had good aesthetics and function. KEY LEARNING POINTS: A supernumerary nonfunctional tooth such as a mesiodens can be successfully used to replace a missing permanent tooth by autotransplantation. Autotransplantation has a high success rate if case selection is good, appropriate surgery is carried out and excellent hygiene is maintained. Autotransplantation should be considered as one of the most biologic techniques for replacing a missing tooth with minimal cost. Autotransplantation can be carried out even after complete root formation in the donor tooth.

Identification of FUS p.R377W in essential tremor.

BACKGROUND AND PURPOSE: Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma (FUS) segregating with essential tremor (ET) within a large French-Canadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated. METHODS: The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing. RESULTS: Sequencing of FUS identified a previously reported non-pathogenic mutation p.G174_G175del in one ET patient and two healthy controls, and a novel p.R377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis. CONCLUSION: This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.

Are pulmonary opacities a marker of pulmonary tuberculosis?

BACKGROUND: On most occasions treatment of pulmonary tuberculosis is started by physicians based predominantly on radiological opacities. Since these opacities may not be suggestive of active pulmonary tuberculosis and most of these opacities may even remain unchanged after complete treatment, starting treatment solely on the basis of these opacities may lead to ambiguous end points of cure. In view of this, study of misdiagnosis of radiological opacities as active pulmonary tuberculosis by physicians was undertaken in one of the respiratory centers of Armed Forces hospitals. METHODS: This was a prospective study of patients referred to our center for confirmation of active disease and institutional therapy. All patients who were diagnosed as pulmonary tuberculosis predominantly on radiological basis by physicians were evaluated for active pulmonary tuberculosis clinically, radiologically and microbiologically. Patients found to have inactive disease were followed for one year. At three monthly review, history, clinical examination, sputum AFB and chest radiographs were done. RESULTS: There were 36 patients [all males, mean age: 36.9 years (range: 22-46 years)]. The most common initial presentation was of asymptomatic persons (33.3%) reporting for routine medical examination. The commonest radiological pattern was localized reticular opacities (52.8%)On follow up, only one patient was diagnosed to have pulmonary tuberculosis. The final diagnosis was consolidation in 6, bronchiectasis in 8, pulmonary tuberculosis in 1 and localized pulmonary fibrosis in 21 patients. CONCLUSION: Diagnosing and treating tuberculosis predominantly on radiological basis is not appropriate and sputum microscopy and culture remains the cornerstone of diagnosing pulmonary tuberculosis.

Low dose methylprednisolone induced bradycardia.

Methylprednisolone induced arrhythmias, especially bradycardia, are well known. Most of the available reports suggest the occurrence of these arrhythmias with high dose intravenous therapy. We, hereby report a case of low dose methylprednisolone induced bradycardia.

Death-associated protein kinase 1 variation and Parkinson's disease.

BACKGROUND AND PURPOSE: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson's disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease. METHODS: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson's disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson's disease, 344 controls) and five separate Caucasian series' (combined sample size 1962 Parkinson's disease patients, 1900 controls). RESULTS: We observed no evidence of association for rs4877365 and rs4878104 and risk of Parkinson's disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. CONCLUSION: These specific DAPK1 intronic variants do not increase the risk of Parkinson's disease. However, further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins.

Recent advances in the role of non-invasive ventilation in acute respiratory failure.

Non-invasive positive pressure ventilation (NIPPV) is the technique of delivering mechanical ventilation without endotracheal intubation or tracheostomy. This is increasingly being utilised in both acute and chronic conditions. Strong evidence supports the use of NIPPV for acute respiratory failure (ARF) to prevent endotracheal intubation (ETI) and to facilitate extubation in patients with acute exacerbations of chronic obstructive pulmonary disease, to avoid ETI in acute cardiogenic pulmonary oedema (ACPO), and in immunocompromised patients. Weaker evidence supports the use of NIPPV for patients with ARF due to asthma exacerbations, with postoperative ARF, pneumonia and acute lung injury/acute respiratory distress syndrome. NIPPV should be applied under close monitoring for signs of treatment failure and, in such cases, ETI should be promptly available. A trained team, at an appropriate location, with careful patient selection and optimal choice of devices can optimise the outcome of NIPPV.

Outcome Analysis of Dual Plating in Management of Unstable Bicondylar Tibial Plateau Fracture - A Prospective Study.

INTRODUCTION: Bicondylar tibial plateau fractures account for 10-30% of tibial plateau fractures. Despite recent advancements in the management of unstable bicondylar tibial plateau fractures, the outcomes are often poor. The present study aimed to evaluate the functional outcomes and complications of internal fixation of bicondylar tibial plateau fractures with the dual plating using two incisions. MATERIALS AND METHODS: The present study included 30 patients (26 males; 4 females, mean age 35.6 years; range, 19 to 65 years) with bicondylar tibial plateau fractures who were treated with dual plating between January 2017 to August 2019. Out of 30 patients, 5 patients had Schatzker type (V) and 25 patients had Schatzker type (VI) bicondylar tibial plateau fracture. All patients were treated with dual plating using two incisions. In all patient's similar standard physical rehabilitation therapy was followed. All complications including intra and post-operative were assessed and recorded. The patients were followed-up for over 24 months. Functional outcomes were assessed with Rasmussen's functional grading system, Oxford knee score, and range of motion of knee joint. Radiological outcomes were evaluated using Rasmussen's radiological scoring system. RESULT: All fractures united with a mean time of 18 weeks. The average knee range of motion was 1.5° - 130° (range: 0° - 10° for extension lag, range: 100° -135° for flexion). Mean Rasmussen's functional grading score at the final follow-up was 26.75. All patients showed excellent or good radiographic results according to Rasmussen's radiological scoring with a mean score of 8.5 (range 6-10). The post-operative radiographs showed mean MPTA was 84.3° and the mean PPTA was 6.2°. In the present study, complications were encountered in five patients. However, there were no cases of secondary loss of reduction, failure of the implant, malunion, or non-union. CONCLUSION: The surgical treatment of bicondylar tibial plateau fractures with dual locking represents a significant treatment option and provides rigid fixation in these fractures with good functional and radiological outcomes.

Meeting the 12 lymph node (LN) benchmark in colon cancer.

BACKGROUND: Examining >or=12 LN in colon cancer has been suggested as a quality metric. The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample. METHODS: Patients with stage I-III disease resected at NCCN centers were identified from a prospective database (n = 718) and were compared to 12,845 stage I-III patients diagnosed in a SEER region. Age, gender, location, stage, number of positive nodes were compared for NCCN and SEER data in regards to number of nodes evaluated. Multivariate logistic regression models were developed to identify factors associated with evaluating 12 LNs. RESULTS: 92% of NCCN and 58% of SEER patients had >or=12 LN evaluated. For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided tumors, stage I disease and BMI >30. CONCLUSIONS: >or=12 LN are almost always evaluated in NCCN patients. In contrast, this target is achieved in 58% of SEER patients. With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control.

Management of primary pulmonary alveolar proteinosis: A multicentric experience.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of surfactant material with reduced lung function and resulting hypoxemia. It is characterized by a variable clinical course, and whole lung lavage (WLL) is the standard treatment. Herein, we report our multicentric experience of management of primary PAP. MATERIALS AND METHODS: This retrospective study included patients with PAP managed at various armed forces respiratory centers from 2009 to 2019. The diagnosis of primary PAP was based on histopathologic confirmation on transbronchial lung biopsy or open lung biopsy and absence of causes of secondary PAP. We analyzed the response to WLL in these patients as well as the safety of the procedure. RESULTS: During the above-specified period, ten patients with a diagnosis of PAP were admitted to various armed forces respiratory centers. The median age of the patients was 34.5 years (range 23-59); there were nine males (90%). The mean duration (± standard deviation) of symptoms was 10.8 (±2.70) months. For management, WLL was done for eight patients with a median volume of 23.5 L (range 18-45) per patient. All the patients showed significant symptomatic response as well as improvement in physiological parameters with no major complications. The median follow-up of all patients was 18 (range 5-44) months. CONCLUSIONS: WLL is a safe, effective therapy in an experienced setting in patients with PAP and provides long-lasting benefits.

Effect of lymph node retrieval rates on the utilization of adjuvant chemotherapy in stage II colon cancer.

BACKGROUND: Failing to meet the benchmark of 12 lymph nodes in resection specimens is an indication for adjuvant chemotherapy in stage II colon cancer. METHODS: Among consecutive eligible patients with pathologic stage II colon cancer treated at eight NCI-designated comprehensive cancer centers between September 1, 2005 and February 19, 2008, we analyzed receipt of adjuvant chemotherapy, with less than 12 versus 12+ lymph nodes removed and examined the primary explanatory variable of interest. RESULTS: Among 258 patients, 46% received adjuvant chemotherapy. An oxaliplatin-containing regimen was used 67% of the time. Younger age (<50 years, P < 0.001), presence of lymphovascular invasion (P = 0.007), and higher T stage (P = 0.007) were independently associated with adjuvant chemotherapy use. There was significant inter-institutional variability in practice with the proportion receiving treatment ranging from 17% to 64% (P < 0.05). Notably, presence of less than 12 lymph nodes in the surgical specimen was a strong predictor of treatment (P = 0.008). CONCLUSIONS: Adjuvant chemotherapy use after resection of stage II colon cancer is common, but by no means standard practice at National Comprehensive Cancer Network (NCCN) institutions. More attention to achieving the recommended benchmark for lymph node dissection has the potential to decrease exposure to the toxicity of adjuvant treatment.

Vascular pathology in male Lewis rats following short-term, low-dose rotenone administration.

The long-term administration of low doses of rotenone has been used to produce a model of Parkinson disease (PD) in rats. However, only about 50% of similarly treated rats develop the PD-like syndrome, with many dying during the first few days of treatment. The lesions in male Lewis rats that became moribund or died after short-term, low-dose rotenone administration are described. Dosed rats had fibrinoid change and acute hemorrhage involving small arteries and arterioles of the brain and lungs. The thalamus, hypothalamus, and medulla oblongata were most frequently and severely affected. Blood vessels in the brain of some male Lewis rats appeared acutely susceptible to the effects of rotenone. Understanding the selective nature of the fibrinoid change and hemorrhage might explain how rotenone produces PD-like signs and lesions in rats, and it might also provide the basis for a model of intraparenchymal hemorrhagic cerebrovascular disease (i.e., hemorrhagic strokes) in humans.

Development of satranidazole mucoadhesive gel for the treatment of periodontitis.

The aim of the paper was to develop satranidazole-containing mucoadhesive gel for the treatment of periodontitis. Different mucoadhesive gels were prepared, using various gelling agents like sodium carboxymethylcellulose (SCMC), poloxamer 407, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the mucoadhesive polymer carbopol 934P. The selected formulations (based on the mucoadhesive force) were studied for different mechanical properties, such as mucoadhesive strength, hardness, compressibility, adhesiveness, and cohesiveness through Texture Profile Analyzer. In vitro satranidazole release from the prepared formulations was also determined and compared with marketed preparation of metronidazole (Metrogyl gel). The formulation SC30 (containing SCMC 3% w/v) showed maximum mucoadhesive strength (167.72 +/- 3.76 g) and adhesiveness (-46.23 +/- 0.34 N mm), with low hardness (9.81 +/- 0.04 N) and compressibility (40.05 +/- 0.48 N mm) and moderate cohesiveness (0.87 +/- 0.01). SC30 formulation exhibited long-term release. Thus, SC30 gel was evaluated for its clinical effectiveness along with marketed metronidazole gel. At the end of the study (42 days of clinical studies), both formulations were found to significantly reduce the probing depth, plaque index, gingival index, calculus criteria, and bleeding index. However, the SC30 gel was more effective in reducing the above parameters than marketed metronidazole gel. This study confirmed the acceptability and effectiveness of satranidazole gel for treatment of periodontitis.

Acute Rejection of a Kidney Transplant in a Patient With Common Variable Immunodeficiency: A Case Report.

Common variable immunodeficiency is a primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. We report a case of a 44-year-old male patient with end-stage renal disease and an established diagnosis of common variable immunodeficiency who underwent a living unrelated kidney transplant. He remained nearly infection free on maintenance immunoglobulin replacement. However, his posttransplant course was complicated by acute rejection that ultimately led to allograft loss. This case illustrates the challenge of transplantation in this patient population because of the delicate balance that must be achieved between maintaining adequate immunosuppression and minimizing the risk of infection.

Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer.

Serological tumor markers have proven valuable in the care of individuals with cancer for the early detection of primary cancers, early detection of cancer relapse, monitoring the response of cancers to therapy, and as predictors of cancer prognosis. Recently, the aberrant hypermethylation of the hMLH1 promoter and its consequent transcriptional silencing has been shown to be a common event in the formation of sporadic microsatellite unstable colon cancer. The silencing of hMLH1 expression appears to be controlled by the hypermethylation of a specific region in the hMLH1 promoter. We developed a methylation-specific PCR assay that assesses this region of the hMLH1 promoter. We found that this assay is able to detect methylated hMLH1 promoter DNA in the serum of some patients with microsatellite unstable colon cancers. In a panel of sera from 19 colon cancer cases, 9 with hMLH1 promoter methylation in the tumor primary, the assay proved 33% sensitive and 100% specific. This assay offers a potential means for the serum-based detection and/or monitoring of microsatellite unstable colon cancers.

Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas.

The transforming growth factor-beta (TGF-beta) type II receptor (RII) is a colon cancer suppressor gene that is inactivated by mutation in 90% of human colon cancers arising via the microsatellite instability (MSI) pathway of carcinogenesis. To determine the pathophysiological consequence of RII mutations, we have determined the timing of their onset among 22 MSI human colon adenomas of varying stages. No RII mutations were detected in any early MSI adenoma, including all those with simple tubular or villous histology. The earliest RII mutation detected was in a region of high-grade dysplasia but was absent from the surrounding simple adenoma. Six additional RII mutations were all found in highly progressed adenomas that contained regions of frankly invasive adenocarcinoma. These RII mutations were detected in both the advanced adenomas and their adjacent regions of carcinoma. RII mutation is a late event in MSI adenomas and correlates tightly with progression of these adenomas to cancer.

Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers.

We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic. Functional analysis confirms that these mutations inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII. The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.