Identification of genomic binding sites and direct target genes for the transcription factor DDIT3/CHOP.

DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 was originally believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Management of early hepatic artery thrombosis following living-donor liver transplantation: feasibility, efficacy and potential risks of endovascular therapy in the first 48 hours post-transplant-a retrospective cohort study.

This retrospective cohort study aims to review our 18-year experience with early hepatic artery thrombosis (e-HAT) following living-donor liver transplantation (LDLT), as well as to assess the feasibility, efficacy and potential risks of endovascular management of e-HAT in the first 48 hours (hrs) post-LDLT. Medical records of 730 patients who underwent LDLT were retrospectively reviewed. In all cases who had developed e-HAT, treatment modalities employed and their outcomes were evaluated. Thirty-one patients developed e-HAT(4.2%). Definite technical success and 1-year survival rates of surgical revascularization[11/31 cases(35.5%)] were 72.7% & 72.7%, whereas those of endovascular therapy[27/31 cases(87.1%)] were 70.4% & 59.3%, respectively. Endovascular therapy was carried out in the first 48hrs post-transplant in 9/31 cases(29%) [definite technical success:88.9%, 1-year survival:55.6%]. Four procedure-related complications were reported in 3 of those 9 cases(33.3%). In conclusion, post-LDLT e-HAT can be treated by surgical revascularization or endovascular therapy, with comparable results. Endovascular management of e-HAT in the first 48hrs post-LDLT appears to be feasible and effective, but is associated with a relatively higher risk of procedure-related complications, compared to surgical revascularization. Hence, it can be reserved as a second-line therapeutic option in certain situations where surgical revascularization is considered futile, potentially too complex, or potentially more risky.

Determination of linagliptin and empagliflozin by UPLC and HPTLC techniques aided by lean six sigma approach.

Two chromatographic techniques were developed and validated for simultaneous determination of the newly co-formulated antidiabetic combination linagliptin and empagliflozin in their pure form and film-coated tables. The first technique was UPLC; the separation and resolution of both analytes were achieved using a Zorbax eclipse plus C18 column applying an isocratic elution based on phosphate buffer pH 4-acetonitrile (65:35, v/v) as a running mobile phase at flow rate 1.5 ml/min and the effluent was monitored at 220 nm. Augmentation of Lean Six Sigma with UPLC and HPTLC methods had a major impact on the development of robust specifications to ensure that the quality at six sigma level has a high level of statistical confidence and target performance. On the chromatogram, empagliflozin and linagliptin appeared at retention times of 1.417 and 2.453 min, respectively. The second technique was HPTLC; both analytes were fairly well resolved and separated using a developing mobile phase composed of ethyl acetate-chloroform-acetonitrile (55:25:20 by volume). The values of retention factor (RF ) were 0.29 and 0.53 for linagliptin and empagliflozin, respectively. All variables were investigated to adjust the whole conditions.

A portal pressure cut-off of 15 versus a cut-off of 20 for prevention of small-for-size syndrome in liver transplantation: A comparative study.

AIM: Portal hypertension has recently been implicated in the pathogenesis of small-for-size syndrome (SFSS) in adult-to-adult living-donor liver transplantation (A-LDLT). The aim of our study is to compare the portal venous pressure (PVP) cut-off values of 15 mmHg and 20 mmHg in terms of prevention of SFSS in A-LDLT. METHODS: Seventy-six patients underwent A-LDLT. A PVP <20 mmHg at the end of the operation was targeted using graft inflow modulation. Patients were divided into two groups: group A, final PVP <15 mmHg; and group B, final PVP 15-19 mmHg. Peak serum bilirubin and peak international normalized ratio in the first month after A-LDLT, as well as hepatic encephalopathy, SFSS, 90-day morbidity, and mortality were observed in both groups. RESULTS: Final PVP was well controlled below 20 mmHg in all patients (group A, n = 39; group B, n = 37). Six patients suffered SFSS in group B (16.2%) compared to one patient (2.6%) in group A (P = 0.04). Nine patients died in group B (24.3%), four of whom died of SFSS, compared to three patients in group A (7.7%) (P = 0.047). CONCLUSION: A PVP cut-off of 15 mmHg seems to be a more appropriate target level than a cut-off of 20 mmHg for prevention of postoperative SFSS in A-LDLT.

Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study.

AIMS/HYPOTHESIS: We addressed the question of whether the autophagy pathway occurs in human peripheral nerves and whether this pathway is associated with peripheral neuropathy in diabetes mellitus. METHODS: By using electron microscopy, we evaluated the presence of autophagy-related structures and neuropathy in the posterior interosseous nerve of patients who had undergone carpal tunnel release and had type 1 or type 2 diabetes mellitus, and in patients with no diabetes (controls). RESULTS: Autophagy-related ultrastructures were observed in the samples taken from all patients of the three groups. The number of autophagy-associated structures was significantly higher (p < 0.05) in the nerves of patients with type 1 than type 2 diabetes. Qualitative and quantitative evaluations of fascicle area, diameter of myelinated and unmyelinated nerve fibres, the density of myelinated and unmyelinated fibres and the g-ratio of myelinated fibres were performed. We found degeneration and regeneration of a few myelinated axons in controls, and a well-developed neuropathy with the loss of large myelinated axons and the presence of many small ones in patients with diabetes. The pathology in type 1 diabetes was more extensive than in type 2 diabetes. CONCLUSIONS/INTERPRETATION: The results of this study show that the human peripheral nerves have access to the autophagy machinery, and this pathway may be regulated differently in type 1 and type 2 diabetes; insulin, presence of extensive neuropathy, and/or other factors such as duration of diabetes and HbA1c level may underlie this differential regulation.

'From highs to lows: a cautionary tale of nitrous oxide recreational use leading to sub-acute combined degeneration of the cord'.

BACKGROUND: Several causes lead to subacute combined degeneration (SACD) of the spinal cord, with nitrous oxide (N2O) inhalation rapidly emerging as the leading cause of functional Vitamin B12 deficiency [1]. CASE PRESENTATION: A 28-year-old man presented with numbness in the extremities and an unstable gait despite having a normal serum Vitamin B12 level. He also disclosed the recreational abuse of N2O. Magnetic Resonance Imaging (MRI) of the cervical spine revealed abnormal signals consistent with SACD. The patient's condition gradually improved after treatment with high dose Vitamin B12. Given the increasing number of N2O-induced SACD cases, the potential for drug abuse requires vigilance from clinicians. CONCLUSION: Healthcare providers are urged to inquire about a patient's history of N2O inhalation to prevent the missed diagnosis of SACD.

Effect of pulsed radiofrequency to the suprascapular nerve (SSN) in treating frozen shoulder pain: A randomised controlled trial.

BACKGROUND: Treatment for frozen shoulder (FS) focuses on pain control and restoring movement and strength through physical therapy. We aimed to evaluate the efficacy of pulsed radiofrequency (PRF) lesioning of the suprascapular nerve for the treatment of FS pain. METHODS: Forty patients with FS were enrolled and randomly assigned into the intervention group (n = 20) that received PRF and a control group (n = 20) which received medical treatment (NSAIDs). Patients were followed-up for a total of three months. The primary outcome was the pain intensity, measured by the Numeric Pain Rating Scale (NRS). The secondary outcomes included shoulder range of motion (ROM) evaluation measured by simple shoulder test (SST); Likert-type-based patient satisfaction scale; and any adverse events (AEs) throughout the treatment period. All results were measured at baseline, at the end of one week, four weeks and 12 weeks after treatment. RESULTS: At 12 weeks post-procedure, the intervention group significantly improved their pain (NRS dropped to 2.80 ± 0.5) and there was significant improvement in range of motion (SST from 6.55% ± 2.0% to 76.50% ± 6.5) compared to control group. CONCLUSIONS: PRF lesioning of the SSN is a fast and effective modality in treating frozen shoulder pain and improving ROM for three months.

Effects of intravenous single-bolus lidocaine infusion versus intravenous single-bolus magnesium sulfate infusion on postoperative pain, emotional status, and quality of life in patients undergoing spine fusion surgery: a randomized study.

BACKGROUND: We assessed the efficiency of intravenous adjuvants in decreasing opioid intake and pain scores after spine fusion surgery. METHODS: This study included 120 patients aged 18-60 listed for spine fusion surgery under general anesthesia. Patients were randomly assigned to four groups: Group (Lidocaine): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min. Group (Magnesium): received IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (combined Lidocaine and Magnesium): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min.+IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (Control): received IV saline 50 mL. The time to the first request analgesia, the postoperative pain score, total analgesic use, patient satisfaction, anxiety, depression, mental state, quality of life, and side effects were measured. RESULTS: The combined group had more extended time for the first analgesic request and fewer rescue analgesia doses than the other groups. NRS scores at rest or movement were statistically significantly lower in the lidocaine group and the combined group compared to the control group (P1, P3<0.05) at almost all times. This combination reduces anxiety and depression and improves overall health up to three months after a single infusion. The combined group had higher patient satisfaction. CONCLUSIONS: A synergistic effect of a combination of lidocaine and magnesium sulfate on perioperative pain was found. It reduces analgesic consumption, depression, and anxiety and improves overall health up to three months after a single infusion dose.

Spectrophotometric Quantitative Analysis of Aspirin and Vonoprazan Fumarate in Recently Approved Fixed-Dose Combination Tablets Using Ratio Spectra Manipulating Tools.

BACKGROUND: Low-dose aspirin (ASP) is prescribed to millions of people around the world as a secondary preventative strategy for the majority of significant cardiovascular events; however, it carries a substantial risk of gastric ulcer and bleeding. Cabpirin® tablets, which include low-dose ASP and vonoprazan fumarate (VON), are approved in Japan for the treatment of acid-related diseases in patients who require a low dose of ASP but are at risk of ASP-associated gastric ulcers. OBJECTIVE: This paper describes the first published quantitative analytical approaches for the determination of ASP and VON. METHOD: The normal ultraviolet absorption spectra of ASP and vonoprazan overlap significantly. The ratio spectra of the studied drugs were created and manipulated by ratio difference (RD) and first derivative of ratio spectra approaches. In the RD approach, the differences in the amplitude values between 229 and 283 nm enabled the quantitative analysis of ASP, and the differences in the amplitude values between 255 and 212 nm enabled the quantitative analysis of vonoprazan. In the first derivative of the ratio spectra approach, the created ratio spectra of each drug were transformed to the first-order derivative. ASP could be determined selectively at 237.40 nm without interference from vonoprazan. Moreover, vonoprazan could be determined selectively at 244 nm without interference from ASP. RESULTS: The applied approaches were validated according to the ICH guideline, with good results. Linear correlations were obtained for ASP and vonoprazan over concentration ranges of 2-25 and 1-10 µg/mL, respectively. CONCLUSIONS: The described methods were optimized, validated, and applied for determination of the studied drugs in the synthetic mixtures and in pharmaceutical tablets without interferences. HIGHLIGHTS: Two spectrophotometric ratio spectra manipulating approaches were developed for the determination of the ASP and vonoprazan in their pharmaceutical combination tablets.

Molecular characterization and second-line antituberculosis drug resistance patterns of multidrug-resistant Mycobacterium tuberculosis isolates from the northern region of South Africa.

Despite South Africa being one of the high-burden multidrug-resistant tuberculosis (MDR-TB) countries, information regarding the population structure of drug-resistant Mycobacterium tuberculosis strains is limited from many regions of South Africa. This study investigated the population structure and transmission patterns of drug-resistant M. tuberculosis isolates in a high-burden setting of South Africa as well as the possible association of genotypes with drug resistance and demographic characteristics. A total of 336 consecutive MDR-TB isolates from four provinces of South Africa were genotyped using spoligotyping and mycobacterial interspersed repetitive-unit-variable number tandem repeat (MIRU-VNTR) typing. Drug susceptibility testing for ofloxacin, kanamycin, and capreomycin was performed using the agar proportion method. The results showed that 4.8% of MDR-TB isolates were resistant to ofloxacin, 2.7% were resistant to kanamycin, and 4.5% were resistant to capreomycin, while 7.1% were extensively drug resistant (XDR), and the remaining 83.6% were susceptible to all of the second-line drugs tested. Spoligotyping grouped 90.8% of the isolates into 25 clusters, while 9.2% isolates were unclustered. Ninety-one percent of the 336 isolates were assigned to 21 previously described shared types, with the Beijing family being the predominant genotype in the North-West and Limpopo Provinces, while the EAI1_SOM family was the predominant genotype in the Gauteng and Mpumalanga Provinces. No association was found between genotypes and specific drug resistance patterns or demographic information. The high level of diversity and the geographical distribution of the drug-resistant M. tuberculosis isolates in this study suggest that the transmission of TB in the study settings is not caused by the clonal spread of a specific M. tuberculosis strain.

Comparison between the BACTEC MGIT 960 system and the agar proportion method for susceptibility testing of multidrug resistant tuberculosis strains in a high burden setting of South Africa.

BACKGROUND: The increasing problem of multi-drug-resistant (MDR) tuberculosis (TB) [ie resistant to at least isoniazid (INH) and rifampicin (RIF)] is becoming a global problem. Successful treatment outcome for MDR-TB depends on reliable and accurate drug susceptibility testing of first-line and second-line anti-TB drugs. METHOD: Consecutive M. tuberculosis isolates identified as MDR-TB during August 2007 to January 2008 using the BACTEC MGIT 960 systems and the agar proportion method were included in this study. Susceptibility testing of MDR-TB isolates against ethambutol (EMB) and streptomycin (STR) as well as two second-line anti-TB drugs, kanamycin (KAN) and ofloxacin (OFX) was performed using the BACTEC MGIT 960 systems at a routine diagnostic laboratory. The results were compared to those obtained by the agar proportion method. RESULT: The agreement between the BACTEC MGIT 960 system and the agar proportion method was 44% for EMB, 61% for STR and 89% for both KAN and OFX. The sensitivity and specificity of the BACTEC MGIT 960 system using the agar proportion method as a gold standard was 92% and 37% for EMB, 95% and 37% for STR, 27% and 97% for KAN and 84% and 90% for OFX, respectively. CONCLUSIONS: The BACTEC MGIT 960 system showed acceptable sensitivity for EMB, STR, and OFX; however, the BACTEC MGIT 960 system was less specific for EMB and STR and demonstrated a low sensitivity for KAN. The lower agreement found between the two methods suggests the unreliability of the BACTEC MGIT 960 system for the drugs tested. The reasons for the lower agreement between the two methods need to be investigated and further studies are needed in this setting to confirm the study finding.

Spectrofluorimetric quantitative analysis of favipiravir, remdesivir and hydroxychloroquine in spiked human plasma.

Favipiravir, remdesivir and hydroxychloroquine have been suggested in COVID-19 Treatment Guidelines Panel of many countries. Synchronous spectrofluorometric measurement provides sensitive tool for resolving the overlapped spectra of multicomponent drugs through converting the wider spectra to narrower sharp spectra. This work introduces the first fluorescence spectroscopic method for quantitative analysis of favipiravir, remdesivir and hydroxychloroquine in spiked human plasma. Testing the fluorescence spectra of favipiravir, remdesivir and hydroxychloroquine shows severe overlap, which hinders the direct quantification of the cited drugs. To overcome the overlapping issue, the drugs under the study have been measured in the synchronous mode at Δλ = 60 nm. Favipiravir could be measured directly at 423 nm without interference of remdesivir or hydroxychloroquine. Synchronous measuring the cited drugs at Δλ = 130 nm with mathematical transforming to the first order derivative spectra allowing remdesivir and hydroxychloroquine at 384 nm and 394 nm, respectively without interference from favipiravir. Different factors affecting the spectrofluorometric measurement process have been verified. The drugs under the study have been successfully quantitatively analyzed in the spiked plasma using the proposed method.

FET fusion oncoproteins interact with BRD4 and SWI/SNF chromatin remodelling complex subtypes in sarcoma.

FET fusion oncoproteins containing one of the FET (FUS, EWSR1, TAF15) family proteins juxtaposed to alternative transcription-factor partners are characteristic of more than 20 types of sarcoma and leukaemia. FET oncoproteins bind to the SWI/SNF chromatin remodelling complex, which exists in three subtypes: cBAF, PBAF and GBAF/ncBAF. We used comprehensive biochemical analysis to characterize the interactions between FET oncoproteins, SWI/SNF complexes and the transcriptional coactivator BRD4. Here, we report that FET oncoproteins bind all three main SWI/SNF subtypes cBAF, PBAF and GBAF, and that FET oncoproteins interact indirectly with BRD4 via their shared interaction partner SWI/SNF. Furthermore, chromatin immunoprecipitation sequencing and proteomic analysis showed that FET oncoproteins, SWI/SNF components and BRD4 co-localize on chromatin and interact with mediator and RNA Polymerase II. Our results provide a possible molecular mechanism for the FET-fusion-induced oncogenic transcriptional profiles and may lead to novel therapies targeting aberrant SWI/SNF complexes and/or BRD4 in FET-fusion-caused malignancies.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Evaluation of TBc identification immunochromatographic assay for rapid identification of Mycobacterium tuberculosis complex in samples from broth cultures.

Tuberculosis (TB) is a disease of major public health concern worldwide, especially in developing countries. In addition, the human immunodeficiency virus (HIV) epidemic has increased the incidence of infection with nontuberculous mycobacteria (NTM). Rapid, accurate, and simple methods for differentiation of Mycobacterium tuberculosis complex (MTBC) isolates from NTM is greatly needed for successful control of the TB epidemic. This study was done to evaluate the clinical performance of the BD MGIT TBc identification test (TBc ID) for rapid identification of MTBC in samples from broth cultures. A total of 229 Ziehl-Neelsen (ZN) stain-positive MGIT cultures were tested using the TBc ID test, and the results were compared with those of the AccuProbe MTBC identification test (GenProbe, San Diego, CA). The agreement between the TBc ID test and the AccuProbe assay was 96% (kappa = 0.92; confidence interval [CI] = 0.869 to 0.971). The sensitivity, specificity, and negative and positive predictive values of the TBc ID test compared to the AccuProbe assay were 100%, 92.4%, 100%, and 92.2%, respectively. After additional molecular testing, the agreement between the two methods increased to 97.8% (kappa = 0.96; CI = 0.917 to 0.994), and the specificity and positive predictive value increased to 95.6% and 95.7%, respectively. The TBc ID test is a simple, sensitive, and specific test for identification of MTBC in samples from acid-fast bacillus (AFB) smear-positive cultures. The TBc ID test could be a good alternative to the AccuProbe test in TB diagnostic laboratories.

Role of the kdpDE Regulatory Operon of Mycobacterium tuberculosis in Modulating Bacterial Growth in vitro.

Bacteria use K+-uptake transporters differentially for adaptation in varying growth conditions. In Mycobacterium tuberculosis, two K+-uptake systems, the Trk comprising the CeoB and CeoC proteins and the Kdp consisting of the two-component system (TCS), KdpDE and KdpFABC, have been characterized, but their selective utilization during bacterial growth has not been completely explored. In the current study, the roles of the M. tuberculosis KdpDE regulatory system alone and in association with the Trk transporters in bacterial growth were investigated by evaluating the growth of M. tuberculosis KdpDE-deletion and KdpDE/Trk (KT)-double knockout mutant strains in planktonic culture under standard growth conditions. The KT-double knockout mutant strain was first constructed using homologous recombination procedures and was evaluated together with the KdpDE-deletion mutant and the wild-type (WT) strains with respect to their rates of growth, K+-uptake efficiencies, and K+-transporter gene expression during planktonic growth. During growth at optimal K+ concentrations and pH levels, selective deletion of the TCS KdpDE (KdpDE-deletion mutant) led to attenuation of bacterial growth and an increase in bacterial K+-uptake efficiency, as well as dysregulated expression of the kdpFABC and trk genes. Deletion of both the KdpDE and the Trk systems (KT-double knockout) also led to severely attenuated bacterial growth, as well as an increase in bacterial K+-uptake efficiency. These results demonstrate that the KdpDE regulatory system plays a key role during bacterial growth by regulating K+ uptake via modulation of the expression and activities of both the KdpFABC and Trk systems and is important for bacterial growth possibly by preventing cytoplasmic K+ overload.

Alpha lipoic acid with pulsed radiofrequency in treatment of chronic lumbosacral radicular pain: A prospective, randomized study.

BACKGROUND: The effect of adding alpha lipoic acid (ALA) to pulsed radiofrequency (PRF) for treatment of lumbar-sacral pain was evaluated. OBJECTIVE: to evaluate the effect of using ALA as an adjuvant therapy with PRF for treatment of chronic lumbosacral radicular pain caused by herniated disc. METHODS: One hundred twenty patients with lumbo-sacral radicular pain allocated into 2 groups. Group I: treated with PRF at 42°C for 120 seconds. Group II: treated as in group I, plus oral ALA 600 mg (Thiotacid 600 mg, EVA PHARMA, Egypt) three times per day (1800 mg/day) for 3 weeks then 600 mg once daily for 2 weeks. The lumbo-sacral radicular pain evaluated using the numerical rating pain score and Oswestry Disability Index. RESULTS: Success rate was significantly higher in group II at 3 and 6 months after intervention. The median values of the numerical rating pain score and the Oswestry Disability Index were significantly lower in group II with no significant difference in Epworth Sleepiness Scale. No major complications were reported in both groups. CONCLUSION: The current study supports the use of ALA with PRF on the dorsal root ganglion for treating lumbosacral radicular pain.

WITHDRAWN: Preoperative duloxetine to prevent postoperative shoulder pain after gynecologic laparoscopy: a randomized controlled trial.

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Early Effects of Laparoscopic Sleeve Gastrectomy and Laparoscopic One-Anastomosis Gastric Bypass on Portal Venous Flow: a Prospective Cohort Study.

BACKGROUND: Portal vein thrombosis (PVT) is an infrequent, yet potentially lethal, complication of bariatric surgery. The aim of this prospective, non-randomized, cohort study is to compare between laparoscopic sleeve gastrectomy (LSG) and laparoscopic one-anastomosis gastric bypass (LOAGB) in terms of their early postoperative effects on portal venous flow and patency. METHODS: Forty-nine morbidly obese patients were allocated to one of 2 groups (A or B). Group A patients underwent LSG, whereas group B patients underwent LOAGB. Portal venous Doppler ultrasound scanning was performed preoperatively and 2 weeks postoperatively in all cases, in order to assess the portal venous flow (PVF) in terms of flow direction and peak systolic velocity (PSV); as well as to assess the portal venous patency and exclude PVT. The mean change in PSV (ΔPSV) and the mean percentage change in PSV (%ΔPSV) were determined in both groups. RESULTS: In all cases (group A (n = 26); group B (n = 23)), the direction of PVF was "hepatopetal" both preoperatively and 2 weeks postoperatively. The mean ΔPSV and the mean %ΔPSV were higher in LSG patients "group A" (- 0.84 cm/s and 3.25% respectively) compared with LOAGB patients "group B"(- 0.06 cm/s and 0.27% respectively); P = 0.038 and 0.039 respectively. The mean change in PSV was in the negative direction in both groups, i.e., "deceleration." No cases of PVT were reported in the study. CONCLUSIONS: Laparoscopic sleeve gastrectomy is associated with greater reduction in portal venous peak systolic flow velocity in the early postoperative period, compared with laparoscopic one-anastomosis gastric bypass.