High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions

Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in the vast majority of patients affected by CATCH 22 syndromes and the Williams-Beuren syndrome, respectively. In a group of 15 Williams- Beuren patients, we have shown previously that a large number of 7q11.23 deletions occur in association with an interchromosomal rearrangement, indicative of an unequal crossing-over event between the two homologous chromosomes 7. In this study, we show that a similar mechanism also underlies the formation of the 22q11.2 deletions associated with CATCH 22. In eight out of 10 families with a proband affected by CATCH 22, we were able to show that a meiotic recombination had occurred at the critical deleted region based on segregation analysis of grandparental haplotypes. The incidences of crossovers observed between the closest informative markers, proximal and distal to the deletion, were compared with the expected recombination frequencies between the markers. A significant number of recombination events occur at the breakpoint of deletions in CATCH 22 patients (P = 2.99x10(-7)). The segregation analysis of haplotypes in three- generation families was also performed on an extended number of Williams-Beuren cases (22 cases in all). The statistically significant occurrence of meiotic crossovers (P = 4.45x10(-9)) further supports the previous findings. Thus, unequal meiotic crossover events appear to play a relevant role in the formation of the two interstitial deletions. The recurrence risk for healthy parents in cases where such meiotic recombinations can be demonstrated is probably negligible. Such a finding is in agreement with the predominantly sporadic occurrence of the 22q11.2 and 7q11. 23 deletions. No parent-of-origin bias was observed in the two groups of patients with regard to the origin of the deletion and to the occurrence of inter- versus intrachromosomal rearrangements.      

Impact of Compensated Cirrhosis Etiology on Postoperative Outcomes Following Total Knee Arthroplasty

BackgroundCirrhotics often demonstrate worse outcomes than their non-cirrhotic counterparts following orthopedic surgery; however, there are limited arthroplasty-focused data on this occurrence. Additionally, variances in postoperative outcomes among the different etiologies of cirrhosis have not been well described. The aim of this study is to evaluate the effect compensated cirrhosis had on postoperative outcomes following elective total knee arthroplasty (TKA).MethodsIn total, 1,734,568 patients who underwent primary TKA from 2006 to 2013 were identified using the Medicare Claims Database. Patients were divided into those with a history of compensated cirrhosis and those with no history of liver disease. Subgroup analysis was performed based on the etiology of cirrhosis. Multivariate logistic regression was used to evaluate postsurgical outcomes of interest.ResultsCirrhotic patients had higher risk of developing disseminated intravascular coagulation (odds ratio [OR] 2.76, P = .003), encephalopathy (OR 3.00, P < .001), and periprosthetic infection (OR 1.79, P < .001) compared to controls. Following subgroup analysis, alcoholic cirrhotics had high risk of periprosthetic infection (OR 2.12, P < .001), fracture (OR 3.28, P < .001), transfusion (OR 2.45, P < .001), and encephalopathy (OR 7.34, P < .001) compared to controls. Viral cirrhosis was associated with an increase in 90-day charges ($14,941, P < .001) compared to controls, while cirrhosis secondary to other causes was associated with few adverse outcomes compared to controls.ConclusionLiver cirrhosis is an independent risk factor for increased perioperative morbidity and financial burden following TKA. Cirrhosis due to etiologies other than viral infections and alcoholism are associated with few adverse outcomes. Surgeons should be aware of these complications to properly optimize postoperative management.     

Cavitary lung lesions and pneumothorax in a healthy patient with active coronavirus-19 (COVID-19) viral pneumonia

Severe respiratory sequelae drive morbidity-associated with coronavirus 2019 (COVID-19) disease. We report a case of COVID-19 pneumonia complicated by cavitary lesions and pneumothorax in a young healthy male. Pneumothorax management with catheter thoracostomy and rapid resolution of the cavitary lesions are described. An extensive work-up for other causes a cavitation was negative and the temporal correlation of the cavities with COVID-19 infection plus their rapid resolution suggest a direct relationship. We propose a mechanism for cavitation secondary to microangiopathy, a cause of cavitation in the vasculitides and a known feature of COVID-19.     

Impact of sociomedical factors on pre-school malnutrition -- an appraisal in an urban setting

The nutritional status of 584 preschool children in an urban slum of Srinagar district was assessed through interviews of mothers conducted in a house-to-house survey, the clinical assessment of child nutritional status, and the anthropometric measurement of the children using accepted standard techniques. The anthropometric measurements of the children were compared to the 50th percentile of the Harvard Standard, while the classification recommended by the Indian Academy of Pediatrics was adopted for the categorization and grading of protein energy malnutrition. 60.45% of the children were malnourished, comprised of 33.22%, 20.89%, and 6.34% of children with grade I, II, and III degrees of malnutrition, respectively. Higher prevalence of malnutrition is associated with higher age, female sex, lower per capita income, higher birth order, and lower parental literacy. Parental literacy status followed by birth order and per capita income were the most important factors associated with preschool child malnutrition.     

Malignant lymphoma of the bladder and female urethra

Primary malignant non-Hodgkin's lymphomas account for 0.4% of malignant neoplasms arising in the bladder and female urethra, but do not comprise a uniform group, and three subgroups can be identified which account for a majority of cases. The most common is a low-grade B-cell lymphoma similar to neoplasms arising in the mucosa-associated lymphoid tissue at other sites — so-called MALTomas. These generally display indolent behavior. A second group accounting for approximately one-fifth of cases is composed almost entirely of large lymphoid cells, and these tumors have a poor prognosis. A third possible group comprises only a few patients who present with diffuse thickening of the bladder wall, and have a poor prognosis. The authors present a new case which suggests that this latter group may be of T-cell origin. In addition to these three subtypes, others no doubt await recognition. The different forms of primary lymphoma appear to require different treatments, and some guidelines are proposed.     

Public health services in Bangladesh with special reference to systems and trends of vital statistics

Health is one of the basic requirements for improvement in the quality of life. Since Bangladesh became independent, a policy for providing essential minimum health care to all has been actively pursued. An overview of Public Health Services in Bangladesh is presented in terms of: (1) a profile of the country, (2) an overview of public health, (3) medical care, and (4) environmental health. Under each of these headings observations are included on recent trends based upon relevant data and information. Finally the authors describe the importance of (1) promotion of health care and planning at the national, divisional, local, and community levels, (2) promotion of medical services at all levels, and (3) effective decentralization of health services to enhance the services of health facilities.     

The effect of hyperbaric oxygen on medial collateral ligament healing in a rat model

Hyperbaric oxygen has been shown to promote healing in bone and some soft tissues. This study was undertaken to determine its effect on ligamentous healing. Forty-eight Sprague-Dawley rats underwent a standardized surgical laceration of the right (divided) medial collateral ligament, whereas the left (undivided) medial collateral ligament was not surgically lacerated. A control group of 24 rats recovered without intervention. An experimental group consisting of the other 24 rats was exposed to hyperbaric oxygen at 2.8 atmospheres for 1.5 hours a day for 5 days after the surgery. Six rats from each group were euthanized at 2, 4, 6, and 8 weeks. The stiffness and final force to failure were recorded for the divided and undivided medial collateral ligaments. At 4 weeks, a statistically greater force was required to cause failure of the previously divided ligaments that had been exposed to hyperbaric oxygen than those that had not. The stiffness and force to cause failure of previously divided ligaments were statistically greater at 4 weeks than at 2 weeks, whether or not hyperbaric oxygen was used. No additional statistical increases in stiffness or force were observed at 6 weeks.     

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.     

A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor

Barbiturate sensitivity was imparted to the human rho1 homooligomeric gamma-aminobutyric acid (GABA) receptor channel by mutation of a tryptophan residue at position 328 (Trp328), which is located within the third transmembrane domain. Substitutions of Trp328 with a spectrum of amino acids revealed that nearly all hydrophobic residues produced receptor channels that were both directly activated and modulated by pentobarbital with similar sensitivities. Previous studies with ligand-gated ion channels (including GABA) have demonstrated that even conservative amino acid substitution within the agonist-dependent activation domain (N-terminal extracellular domain) can markedly impair agonist sensitivity. Thus, the lack of significant variation in pentobarbital sensitivity among the Trp328 mutants attests to an intrinsic difference between pentobarbital- and the GABA-dependent activation domain. Compared with the heterooligomeric alphabetagamma receptor channel, the mode of modulation for homooligomeric Trp328 mutants by pentobarbital was more dependent on the GABA concentration, yielding potentiation only at low concentrations of GABA (fractions of their respective EC50 values), yet causing inhibition at higher concentrations. Agonist-related studies have also demonstrated that residue 328 plays an important role in agonist-dependent activation, suggesting a functional interconnection between the GABA and pentobarbital activation domains.