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Hisham A Mosli,1 Hala H Mosli,2 Akram A Bokhari1 1Department of Urology, 2Department of Internal Medicine (Endocrinology), King Abdulaziz University Hospital, Jeddah, Saudi Arabia Objective: To establish a possible association between obesity, measured by waist circumference (WC) and body mass index (BMI), and voiding and sexual functions in a random cohort of Saudi men. Materials and methods: An outpatient men’s health clinic was set up at King Abdulaziz University Hospital in Jeddah, Saudi Arabia and men were invited to discuss their sexual and urinary functions. The data collected included age, WC, weight, height, blood pressure, history of diabetes, hypertension, and smoking. The International Prostate Symptom Score (IPSS) and the International Inventory of Erectile Function (IIEF-5) questionnaire were used to assess urinary tract symptoms and sexual function, respectively. Serum testosterone, prostate-specific antigen and cholesterol levels were measured and documented. Data were analyzed using the Statistical Package for the Social Sciences. Results: We recruited 113 participants. The mean WC and BMI of the men were 104 ± 14.599 cm and 29.706 kg/m2, respectively. Thirty-seven men (32.7%) had an IPSS ≥ 8 points. Sexual disorders were reported in 19 men; 16 men had erectile dysfunction, while three had premature ejaculation. Of the whole cohort, 37 men were diabetic, of which 15 (40.5%) had an IPSS ≥ 8 and 13 (35%) were either overweight or obese. Conclusion: Increased WC and BMI were associated with diabetes mellitus and large percentages of voiding and sexual disorders. Keywords: obesity, waist circumference, body mass index, voiding function, sexual function

Objectives: This study aimed to evaluate the common clinical diagnoses and treatment management of acute respiratory infections (ARIs) in children and determine when antibiotics are recommended and prescribed., Methods: A retrospective review of medical charts was carried out at King Salman Bin Abdulaziz Medical City (KSAMC) Hospital to assess pediatric patients diagnosed with ARIs aged 0-14 years, excluding those requiring antibiotics for conditions other than ARIs. Data, including demographic diagnoses and treatment management, were extracted using consecutive sampling, and statistical analyses were conducted using Jamovi software., Results: A total of 285 pediatric patients were included, with a median age of 3 (IQR = 1-6) years and a male predominance of 59.2%. Bronchopneumonia was the most common respiratory disease, diagnosed in 39.1% of participants. The median durations for illness and hospital admission were four and three days, respectively. Clinical evaluations showed an average respiratory rate of 28±10.5 breaths per minute and a mean oxygen saturation of 96.4±3.46% through pulse oximetry. The use of antibiotics was commonly prescribed in ARI patients only when accompanied by certain bacterial infections (46.32%)., Conclusions: ARIs are a common viral health issue among children, emphasizing that not all ARIs in children are caused by bacteria and that antibiotics should only be used when there is a bacterial infection present. Enhanced diagnostic precision, patient awareness, and provider education are the global community's recommendations to prevent the presence of antibiotic resistance and the irrational use of antibiotics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alharbi et al.)

Background and Objective: Identification of clinical characteristics and risk factors for mortality in COVID-19 is important for early detection and precise case management. The study aimed to describe the sociodemographic, clinical, and laboratory characteristics of in-hospital COVID-19 deaths in Almadinah Almonawarah city, Saudi Arabia, and to identify risk factors for early mortality among them., Methods: This is an analytical cross-sectional study. The main outcomes were demographic and clinical characteristics of COVID 19 patients who died from March till December 2020, during the hospital stay. We collected 193 records of COVID-19 patients, from two major hospitals in Al Madinah region, Saudi Arabia. Descriptive and inferential analysis were performed to identify and relate the factors of early death., Results: Out of the total deaths, 110 died during the first 14 days of admission (Early death group) and 83 died after 14 days of admission (Late death group). Early death group had a significantly higher percentages of old age patients (p=0.027) and males (72.7%). Comorbidities were found in 166 (86%) of cases. Multimorbidity were significantly higher in early deaths than in late deaths 74.5% (p=<0.001). Women had significantly higher mean values of CHA2SD2 comorbidity scores (3.28 versus 1.89 for men; p <0.001). Moreover, predictors of high comorbidity scores were older age (p=0.005), higher respiratory rate (p=0.035), and raised alanine transaminase (p=0.047)., Conclusion: Old age, comorbid illness, and severe respiratory involvement were prevalent among COVID-19 deaths. Comorbidity scores were significantly higher in women. Comorbidity was found to be significantly more associated with early deaths., Competing Interests: Conflict of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.

Introduction: Echinoderm microtubule-associated protein-like 4 (EML4)-Anaplastic Lymphoma Kinase (ALK) rearrangements occur in 3% to 7% of lung adenocarcinomas and are targets for treatment with tyrosine kinase inhibitors (TKIs). Here we have developed three novel EML4-ALK-positive patient-derived Non-Small-Cell-Lung-Cancer (NSCLC) cancer cell lines, CUTO8 (variant 1), CUTO9 (variant 1) and CUTO29 (variant 3) and included a fourth ALK-positive cell line YU1077 (variant 3) to study ALK-positive signaling and responses. Variants 1 and 3 are the most common EML4-ALK variants expressed in ALK-positive NSCLC, and currently cell lines representing these EML4-ALK variants are limited., Materials and Methods: Resazurin assay was performed to evaluate cell viability. Protein levels were determined using western blotting. RNA sequencing was performed in all four cell lines to identify differentially expressed genes. Whole-genome sequencing was performed to determine the presence of EML4-ALK fusion and ALK tyrosine kinase inhibitor resistance mutations., Results: In this study, we have confirmed expression of the corresponding ALK fusion protein and assessed their sensitivity to a range of ALK tyrosine kinase inhibitors. These patient derived cell lines exhibit differential sensitivity to lorlatinib, brigatinib and alectinib, with EML4-ALK variant 3 containing cell lines exhibiting increased sensitivity to lorlatinib and brigatinib as compared to alectinib. These cell lines were further characterized by whole genome sequencing and RNA-seq analysis that identified the ribonucleotide reductase regulatory subunit 2 (RRM2) as a downstream and potential therapeutic target in ALK-positive NSCLC., Conclusion: We provide a characterization of four novel EML4-ALK-positive NSCLC cell lines, highlighting genomic heterogeneity and differential responses to ALK TKI treatment. The RNA-Seq characterization of ALK-positive NSCLC CUTO8, CUTO9, CUTO29 and YU1077 cell lines reported here, has been compiled in an interactive ShinyApp resource for public data exploration (https://ccgg.ugent.be/shiny/nsclc&#95;rrm2&#95;2022/)., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background Urolithiasis is the formation of calculi in the urinary system. It is a public health concern worldwide that can lead to serious long-term consequences. Age, gender, dietary habits, and physical activity levels are all factors that increase the risk of urolithiasis formation. Furthermore, the presence of comorbid medical conditions such as diabetes and hypertension are other major risk factors. Among the most prominent determinants that raise the likelihood of acquiring urolithiasis is exposure to high temperatures, especially in middle-aged men. Consequently, Saudi residents are two and a half times more prone than the global average to develop urolithiasis, especially those in the Kingdom's hottest regions. Methodology This cross-sectional study assessed the self-reported prevalence and non-nutritional risk factors of urolithiasis among the population of Hail, Saudi Arabia, through an electronic questionnaire. The questionnaire contained 16 questions divided into three categories. Participants' permission was obtained before completing the questionnaire. The Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA) was used to analyze the data. Results Of the 1150 participants with a mean age of 26.3 ± 12.8 years old, nearly half were males (50.9%). Urolithiasis was detected among 158 (13.7%) participants. The following factors showed significant relation with having urolithiasis: increased age, male gender, a low level of education, diabetes, hypertension, and hyperthyroidism. A family history of renal stones was also associated with double the risk of having urolithiasis. Conclusion The results showed a high prevalence of urolithiasis in the Hail region, with many risk factors associated with it. It is important to support and promote awareness campaigns that address the critical risk factors of urolithiasis. Further studies should be conducted to arrive at a better understanding of the association between non-nutritional risk factors and developing urolithiasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bokhari et al.)

Summary: This report describes an isolated urethral duplication in the coronal plane in a child referred with primary 'enuresis'. This presentation is unique because duplications usually occur in the sagittal plane. In patients with suspected urethral duplication, magnetic resonance imaging in conjunction with catheterisation of the distal duplicate opening accurately delineates the abnormality, so that individualised treatment strategies can be considered., (Copyright© Authors.)

Recent data suggest that the transcription factor Zfp148 represses activation of the tumor suppressor p53 in mice and that therapeutic targeting of the human orthologue ZNF148 could activate the p53 pathway without causing detrimental side effects. We have previously shown that Zfp148 deficiency promotes p53-dependent proliferation arrest of mouse embryonic fibroblasts (MEFs), but the underlying mechanism is not clear. Here, we showed that Zfp148 deficiency downregulated cell cycle genes in MEFs in a p53-dependent manner. Proliferation arrest of Zfp148-deficient cells required increased expression of ARF, a potent activator of the p53 pathway. Chromatin immunoprecipitation showed that Zfp148 bound to the ARF promoter, suggesting that Zfp148 represses ARF transcription. However, Zfp148 preferentially bound to promoters of other transcription factors, indicating that deletion of Zfp148 may have pleiotropic effects that activate ARF and p53 indirectly. In line with this, we found no evidence of genetic interaction between TP53 and ZNF148 in CRISPR and siRNA screen data from hundreds of human cancer cell lines. We conclude that Zfp148 deficiency, by increasing ARF transcription, downregulates cell cycle genes and cell proliferation in a p53-dependent manner. However, the lack of genetic interaction between ZNF148 and TP53 in human cancer cells suggests that therapeutic targeting of ZNF148 may not increase p53 activity in humans.

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4 + and CD8 + T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT 50 ) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4 + but not CD8 + T cell responses; patients with higher PRNT 50 and CD4 + T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8 + T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8 + T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed higher levels of CYP24A1 than immortalized endometrial epithelial cells. RT-PCR and Western blotting were used to examine CYP24A1 mRNA and protein levels in endometrial cancer cells after 8, 24, 72, and 120 h of exposure to progesterone, progestin derivatives and calcitriol, either alone or in combination. Progestins inhibited calcitriol-induced expression of CYP24A1 and splice variant CYP24SV mRNA and protein in cancer cells. Furthermore, actinomycin D, but not cycloheximide, blocked calcitriol-induced CYP24A1 splicing. siRNA-induced knockdown of CYP24A1 expression sensitized endometrial cancer cells to calcitriol-induced growth inhibition. These data suggest that CYP24A1 overexpression reduces the antitumor effects of calcitriol in cancer cells and that progestins may be beneficial for maintaining calcitriol's anti-endometrial cancer activity.

Nestin, an intermediate filament protein and a stem cell marker is expressed in several tumors. Until recently, little was known about the expression levels and the role of Nestin in endometrial cancer. Compared to the immortalized endometrial epithelial cell line EM-E6/E7-TERT, endometrial cancer cell lines express high to moderate levels of Nestin. Furthermore, endometrial tumors and tumor cell lines have a cancer stem-like cell subpopulation expressing CD133. Among the cancer lines, AN3CA and KLE cells exhibited both a significantly higher number of CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE increased cells in G0/G1 phase of the cell cycle, whereas overexpression in Ishikawa decreased cells in G0/G1 phase and increased cells in S-phase. Nestin knockdown cells showed increased p21, p27, and PNCA levels and decreased expression of cyclin-D1 and D3. In contrast, Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by downregulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating the epithelial cell marker E-cadherin whereas the opposite was observed with Nestin overexpressing Ishikawa cells. Nestin knockdown also inhibited, while overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo. Finally, progesterone inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment.

Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC) mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel's structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing.

Transforming growth factor-β (TGF-β), regulates cell proliferation, angiogenesis, metastasis, and is an inducer of epithelial-mesenchymal transition (EMT). Cancer cells exhibit activated TGF-β/SMAD signaling pathway and its inhibition is an attractive strategy for cancer treatment. The Chinese Herbs Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC) have been shown to be beneficial to cancer patients, but the mechanisms by which the extracts of two herbs elicit the beneficial effects are unclear. In this study, we have used human endometrial cancer cells to assess the anticancer efficacy of SB and FC on TGF-β signaling pathway components. SB and FC treatment of cancer cells resulted in a significant decrease in expression of TGF-β isoforms, TGF-β receptors, and SMADs. Both herbs effectively inhibited basal and TGF-β1-induced cancer cell proliferation and invasion, which was accompanied with abrogation of Snail, Slug, matrix metalloproteinases (MMPs), αvβ3 integrin, focal adhesion kinase (FAK), and p-FAK expression. An inhibitor of TGF-βRI blocked TGF-β1-induced cell invasion and significantly diminished antitumor effects of SB and FC. These results suggest that SB and FC block endometrial cancer growth by downregulating TGF-β/SMAD signaling pathway., (© 2015 Wiley Periodicals, Inc.)

The herbs Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC) are widely used in Chinese medicine to treat several aliments and as an adjuvant to chemotherapy of lung cancer. No information is available regarding the two herbs' influence on ovarian and endometrial cancer. To fill this data gap we compared cell growth responses to SB and FC in ovarian and endometrial cancer cell lines. Dose-dependent cell growth inhibition was observed following higher doses in all cell lines while lower doses stimulated growth in only endometrial cell lines. Higher doses of SB and FC significantly decreased cell growth on soft agar and decreased the invasive potential of cancer cells. Treatment of cells with both herbs resulted in activation of caspase-3, G0 /G1 phase cell cycle arrest, downregulation of cyclins D1 and D3 and induction of p27. Both herbs decreased NFκB DNA binding, reduced expression of phosphorylated IκBα, abrogated NFκB activation, and downregulated NFκB-regulated metastasis-promoting proteins in cancer cells. Furthermore, knockdown of NFκB attenuated SB- and FC-induced cell growth inhibition. These results suggest that inhibition of NFκB activation may be an important mechanism for growth suppression by SB and FC. Data indicate that these herbs may represent a new source of agents for NFκB inhibition in cancer therapy., (© 2013 Wiley Periodicals, Inc.)

Increased expression of TGFβ isoforms in human endometrial cancer correlates with decreased survival and poor prognosis. Progesterone has been shown to exert a chemoprotective effect against endometrial cancer, and previous animal models have suggested that these effects are accompanied by changes in TGFβ. The goal of this study was to characterize the effect of progesterone on TGFβ signaling pathway components and on TGFβ-induced protumorigenic activities in endometrial cancer cell lines. Progesterone significantly decreased expression of three TGFβ isoforms at 72 hours after treatment except for TGFβ2 in HEC-1B and TGFβ3 in Ishikawa cells. Progesterone treatment for 120 hours attenuated expression of the three isoforms in all cell lines. Progesterone exposure for 72 hours reduced expression of TGFβ receptors in HEC-1B cells and all but TGFβR1 in Ishikawa cells. Progesterone reduced TGFβR3 expression in RL-95 cells at 72 hours, but TGFβR1 and βR2 expression levels were not affected by progesterone at any time point. SMAD2/3 and pSMAD2/3 were substantially reduced at 72 hours in all cell lines. SMAD4 expression was reduced in RL-95 cells at 24 hours and in HEC-1B and Ishikawa cells at 72 hours following progesterone treatment. Furthermore, progesterone effectively inhibited basal and TGFβ1-induced cancer cell viability and invasion, which was accompanied by increased E-cadherin and decreased vimentin expression. An inhibitor of TGFβRI blocked TGFβ1-induced effects on cell viability and invasion and attenuated antitumor effects of progesterone. These results suggest that downregulation of TGFβ signaling is a key mechanism underlying progesterone inhibition of endometrial cancer growth., (©2014 American Association for Cancer Research.)

Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC), an unusual ion channel linked to the conserved clag gene family. Although PSAC recognizes and transports a broad range of uncharged and charged solutes, it must efficiently exclude the small Na(+) ion to maintain infected cell osmotic stability. Here, we examine possible mechanisms for this remarkable solute selectivity. We identify guanidinium as an organic cation with high permeability into human erythrocytes infected with Plasmodium falciparum, but negligible uptake by uninfected cells. Transport characteristics and pharmacology indicate that this uptake is specifically mediated by PSAC. The rank order of organic and inorganic cation permeabilities suggests cation dehydration as the rate-limiting step in transport through the channel. The high guanidinium permeability of infected cells also allows rapid and stringent synchronization of parasite cultures, as required for molecular and cellular studies of this pathogen. These studies provide important insights into how nutrients and ions are transported via PSAC, an established target for antimalarial drug development.

Development of malaria parasites within vertebrate erythrocytes requires nutrient uptake at the host cell membrane. The plasmodial surface anion channel (PSAC) mediates this transport and is an antimalarial target, but its molecular basis is unknown. We report a parasite gene family responsible for PSAC activity. We used high-throughput screening for nutrient uptake inhibitors to identify a compound highly specific for channels from the Dd2 line of the human pathogen P. falciparum. Inheritance of this compound's affinity in a Dd2 × HB3 genetic cross maps to a single parasite locus on chromosome 3. DNA transfection and in vitro selections indicate that PSAC-inhibitor interactions are encoded by two clag3 genes previously assumed to function in cytoadherence. These genes are conserved in plasmodia, exhibit expression switching, and encode an integral protein on the host membrane, as predicted by functional studies. This protein increases host cell permeability to diverse solutes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The plasmodial surface anion channel (PSAC) is an unusual small-conductance ion channel induced on erythrocytes infected with plasmodia, including parasites responsible for human malaria. Although broadly available inhibitors produce microscopic clearance of parasite cultures at high concentrations and suggest that PSAC is an antimalarial target, they have low affinity for the channel and may interfere with other parasite activities. To address these concerns, we developed a miniaturized assay for PSAC activity and carried out a high-throughput inhibitor screen. Approximately 70,000 compounds from synthetic and natural product libraries were screened, revealing inhibitors from multiple structural classes including two novel and potent heterocyclic scaffolds. Single-channel patch-clamp studies indicated that these compounds act directly on PSAC, further implicating a proposed role in transport of diverse solutes. A statistically significant correlation between channel inhibition and in vitro parasite killing by a family of compounds provided chemical validation of PSAC as a drug target. These new inhibitors should be important research tools and may be starting points for much-needed antimalarial drugs.

Human erythrocytes infected with the malaria parasite Plasmodium falciparum have increased permeabilities to many solutes. The plasmodial surface anion channel (PSAC) may mediate these changes. Despite good understanding of the biochemical and biophysical properties, the genetic basis of PSAC activity remains unknown. Functional polymorphisms in laboratory isolates and two mutants generated by in vitro selection implicate a parasite-encoded channel, although parasite-induced modifications of endogenous channels have not been formally excluded. Here, we identified stable differences in furosemide efficacy against PSAC activity induced by HB3 and 3D7A parasites. This difference was apparent in both single PSAC patch-clamp recordings and in sorbitol-mediated osmotic lysis measurements, confirming that Cl(-) and sorbitol are transported by a single-channel type. Examination of 19 progeny from a genetic cross between HB3 and 3D7A revealed complex inheritance with some cloned progeny exhibiting furosemide affinities outside the range of parental values. Isolates generated by selfing of the 3D7A clone also exhibited altered furosemide affinities, implicating changes in one or more alleles during meiosis or passage through a primate host. PSAC may be encoded by multiple parasite genes (e.g. a multi-gene family or multiple genes that encode distinct channel subunits) or a single polymorphic gene under strong selective pressure.

The plasmodial surface anion channel (PSAC) is a voltage-dependent ion channel on erythrocytes infected with malaria parasites. To fulfill its presumed function in parasite nutrient acquisition, PSAC is permeant to a broad range of charged and uncharged solutes; it nevertheless excludes Na(+) as required to maintain erythrocyte osmotic stability in plasma. Another surprising property of PSAC is its small single-channel conductance (<3 pS in isotonic Cl(-)) in spite of broad permeability to bulky solutes. While exploring the mechanisms underlying these properties, we recently identified interactions between permeating solutes and PSAC inhibitors that suggest the channel has more than one route for passage of solutes. Here, we explored this possibility with 22 structurally diverse solutes and found that each could be classified into one of two categories based on effects on inhibitor affinity, the temperature dependence of these effects and a clear pattern of behavior in permeant solute mixtures. The clear separation of these solutes into two discrete categories suggests two distinct mechanisms of transport through this channel. In contrast to most other broad-permeability channels, selectivity in PSAC appears to be complex and cannot be adequately explained by simple models that invoke sieving through rigid, noninteracting pores.

Torsion of the greater omentum is a rare condition with symptoms resemble those of acute appendicitis and is infrequently diagnosed preoperatively. Treatment is surgical excision. Laparoscopic approach is an excellent diagnostic and therapeutic tool.

We carried out a retrospective and prospective study of 67 patients who had sustained hand injuries from punching glass over a period of 33 months. All had consumed alcohol and had argued with a partner. The mean age was 25 years, 90% were male and 56% were unemployed. Seventy per cent of injuries occurred between 23.00 and 04.00 hours. Total damage included division of 149 tendons, 33 nerves and nine arteries. Fifty-two per cent of patients required admission for more than 1 day. The mean number of follow-up visits was 3.6 and the majority needed hand therapy and occupational therapy services. Cost per injury was estimated as 1,120 pounds. Such injuries cause major disability in an already disadvantaged section of society. The challenge is to educate the susceptible patient group.