Regular cold shower exposure modulates humoral and cell-mediated immunity in healthy individuals.

BACKGROUND: Cold hydrotherapy is an ancient practice that has recently gained scientific interest for its potential health benefits. This study explored the effects of regular cold shower exposure on immune cell function. METHODS: Sixty healthy Egyptian adults were randomized to take cold or hot showers daily for 90 days. Levels of immunoglobulins, cytokines, and interferon-gamma were measured in blood samples at baseline, 30, 60, and 90 days. RESULTS: The cold shower group exhibited significant increases in immunoglobulin levels. Conversely, the hot shower group showed a significant decrease in IgM levels at 60 and 90 days compared to baseline, alongside nonsignificant decrease of IgG and IgA. the cold shower group demonstrated elevated levels of IL-2 and IL-4 at 90 days, indicating enhanced T-cell proliferation and humoral immunity, respectively. In contrast, the hot shower group did not exhibit significant changes in cytokine levels. There were no significant differences in IFN-γ and TNF-α levels between the groups. CONCLUSIONS: Regular cold shower exposure appears to enhance humoral and cell-mediated immunity through the upregulation of antibodies, interleukin-2, and interleukin-4. Brief cold stressors may induce physiological adaptations that prime the immune response. This accessible, sustainable lifestyle modification could potentially serve as an alternative therapy to boost immunity. Further research on larger populations is warranted to better understand the physiological effects of cold temperatures on immunity.

HYDIN variants cause primary ciliary dyskinesia in the Finnish population.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell. Thus far, disease causing variants in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management. METHODS: Whole exome sequencing was used to identify disease causing variants in Finnish PCD cohort. The effect of the identified HYDIN variants on cilia structure and function was confirmed by high-speed video analysis, immunofluorescence and electron tomography. RESULTS: In this study, we identified three Finnish PCD patients carrying homozygous loss-of-function variants and one patient with compound heterozygous variants within HYDIN. The functional studies showed defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections, associated with mostly static airway cilia. CONCLUSION: Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different national populations.

Marginal adaptation of customized gutta percha cone with calcium silicate based sealer versus MTA and biodentine apical plugs in simulated immature permanent teeth (an in vitro study).

BACKGROUND: This study aimed to compare the marginal adaptation of a single customized gutta percha cone with calcium silicate-based sealer versus mineral trioxide aggregate (MTA) and Biodentine apical plugs in simulated immature permanent teeth. METHODS: Thirty-nine extracted human maxillary anterior teeth were selected, prepared to simulate immature permanent teeth with an apical diameter 1.1 mm, placed in moist foam and divided into three groups. Group 1: Obturation with a single customized gutta percha cone and calcium silicate sealer. Group 2: MTA apical plug. Group 3: Biodentine apical plug. After incubation, teeth were horizontally sectioned at 1 mm and 3 mm from the apex and marginal adaptation was evaluated using scanning electron microscope (SEM). RESULTS: Biodentine showed the least mean gap size at both 1 and 3 mm from the apex with no statistically significant differences compared to MTA (p > 0.05). The single customized cone with calcium silicate based sealer showed the greatest mean gap size at both 1 and 3 mm from the apex with a statistically significant difference compared to the other groups (p < 0.001). CONCLUSION: Biodentine and MTA apical plugs provide a significantly better marginal adaptation to the dentinal walls than a single customized gutta percha cone with calcium silicate based sealer in simulated immature permanent teeth.

Road Traffic Accident Traumatic Vehicle Seat Belt Abdominal Wall Hernia.

Traumatic abdominal wall hernia (TAWH) is a rare type of hernia with an incidence of about <1.5%, resulting from blunt abdominal trauma, which leads to an increase in the intra-abdominal pressure and rupture in the abdominal musculature and fascia with herniation of the abdominal organs into the defect. Most TAWH contained either a small bowel (69%) or a large bowel (36%), with 16% containing both. This condition is often not present as an isolated case, as 30% to 60% of the cases are accompanied by other intra-abdominal injuries. The typical manner of presentation is a tender subcutaneous swelling across the abdomen wall with overlaying bruising and ecchymosis. The radiological investigative modality of CT scan has the highest index of diagnosing accompanied intra-abdominal visceral injuries. We present a rare case of a 23-year-old male patient diagnosed with TAWH containing both small bowel and sigmoid colon associated with psoas hematoma caused by a seat belt postroad traffic accident (RTA).

Adsorption rate of uranium and thorium isotopes in soil and plants grown in a high background radiation area.

An important method for measuring radionuclide activity is alpha spectrometry. Ten soil samples were collected from the studied area. The activity concentrations of 238U and 234U in the collected soil samples ranged between 135 and 218 Bq kg-1 and between 117 and 183 Bq kg-1, respectively. 232Th, 230Th and 228Th activity concentrations ranged between 101 and 339, between 122 and 234 and between 106 and 385 Bq kg-1, respectively. When calculating the amount of radionuclide transport across the food chain, assessment models usually employ a transfer factor. Through root uptake, U and Th are transferred from the soil to food plants. To monitor the movement of radionuclides from the uranium series in diverse environments, it may be possible to use the ratios of uranium and thorium isotopes. Uranium mobility in soil depends on different physicochemical, organic and enzymatic factors and mechanisms. The high mobility of uranium is the main reason for the accumulation of uranium in the soil at root level and the possibility of its transfer to plants. A group of plants were selected that are grown in this area and the population relies on them mainly to meet their food needs. The concentration and transfer factor values of uranium isotopes were the highest in roots as compared with leaves and stems. Uranium in plants accumulates in roots and is then transferred to leaves. The mobility of uranium in plant tissues is constrained because it frequently adsorbs cell wall components. As a result, concentrations are frequently higher in tissues located in lower parts of the plant, with root surfaces having the highest concentrations.

Side-specific factors for intraoperative hemodynamic instability in laparoscopic adrenalectomy for pheochromocytoma: a comparative study.

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

Cardiac biomarkers as tools in the prediction and diagnosis of traumatic pericarditis and traumatic reticuloperitonitis in cattle and buffaloes.

BACKGROUND: In the livestock industry, Foreign Body Syndrome is a devastating disease condition. Feeding management, lacking of food discrimination, and eating chopped food increase the risk of swallowing sharp foreign bodies in bovine species. In addition to the honeycomb cells shape of the reticulum, the contractions of the reticular wall, gravid uterine pressure, and parturition efforts, foreign bodies can penetrate the reticular wall, causing cascade of problems including traumatic reticulitis, traumatic reticuloperitonitis, and traumatic pericarditis. The present study was carried out to evaluate the diagnostic significance of cardiac troponin I rapid test cassette and other cardiac biomarkers including serum cardiac troponin I (cTn I), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase enzyme (AST), in confirmed cases of traumatic pericarditis (TP) and/or traumatic reticuleoperitonitis (TRP) in cattle and buffaloes. METHODS: A total number of 30 animals (22 cattle and 8 buffaloes) with different signs such as anorexia, jugular distension, brisket edema, and signs of pain (reluctance to move, arching back, and abduction of the forelimbs) were included in the present study. Based on case history, clinical signs, ferroscopic, pericardiocentesis, radiographic and ultrasonographic examinations, TP were confirmed in cattle (n = 10) and buffaloes (n = 8) while TRP were confirmed only in cattle (n = 12). Additionally, 20 clinically healthy animals (n = 10 cattle and 10 buffaloes) were used as a control group. Blood samples were collected for determination of blood level of Tn-I, and activity of CK-MB, LDH, and AST. RESULTS: The obtained results revealed a highly significant increase in serum cTn I in diseased cattle with TP and TRP (P = 0.00), while buffaloes with TP showed no significant changes in serum cTn I (P = 0.111). Both diseased cattle and buffaloes showed increased serum activities of CK-MB, AST, and LDH enzyme. On the other hand, cardiac troponin I rapid test cassette failed to detect cTn I in diseased animals. CONCLUSION: The study concluded that the cardiac troponin I rapid test cassette did not have a diagnostic significance and could not be used as a point-of-care under field condition for diagnosis of TP and TRP in large ruminants. However, the serum troponin I level is helpful in diagnosis of TP and TRP in cattle. Although cardiac biomarkers have some diagnostic values in TP and TRP, the traditional diagnostic methods (clinical, radiography and ultrasonography examinations) are crucial for thorough evaluation of TP/TRP cases in bovine.

Perforated neonatal appendicitis mimicking necrotizing enterocolitis in a premature neonate: a case report and literature review.

Necrotizing enterocolitis (NEC) predominantly affects preterm infants and can mimic other conditions like acute appendicitis. Neonatal appendicitis (NA) is extremely rare, with an incidence of 0.04-0.2% and high fatality rates. Due to its rarity and resemblance to other neonatal conditions, NA diagnosis is often delayed. We report a case of a 2220-g male preterm neonate delivered at 31 + 5 weeks via urgent cesarean section due to chorioamnionitis, initially misdiagnosed with NEC but later found to have a perforated appendix. The neonate recovered well post-surgery, with the ileostomy reversed 10 weeks later. Prompt surgical intervention is crucial for NA, as it requires different management than NEC. This case underscores the importance of considering NA in preterm infants with severe abdominal symptoms and emphasizes timely surgical intervention to improve outcomes. Additionally, it supports the hypothesis that localized NEC involving the appendix may have a better prognosis than generalized NEC.

Ceftriaxone-induced symptomatic cholelithiasis in a child: case report and literature review.

Ceftriaxone is a third-generation cephalosporin. Due to its wide range of activity and acceptable safety profile, it is frequently prescribed to paediatric patients. However, there are several documented cases of reports of uncommon adverse events, such as cholecystitis, linked to the use of ceftriaxone. This study discusses the case of an 8-year-old female patient who developed cholecystitis, an inflammation of the gallbladder, after being treated with ceftriaxone. The patient presented with right upper quadrant pain, associated with nausea. Imaging studies showed the presence of stones and shadowing sludge, leading to acute inflammation of the gallbladder. Prompt cessation of ceftriaxone and supportive treatment led to the resolution of cholecystitis and the complete disappearance of the sludge and stones. The study highlights that early identification and withdrawal of the antibiotic can lead to successful therapy and the avoidance of unnecessary surgical procedures.

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs.

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades.

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront auto-SCT over the past three decades, including those with high-risk disease.

Microbial Adhesion to Different Thermoplastic Denture Base Materials in Kennedy Class I Partially Edentulous Patients.

Introduction Since the polished and fitting surface of the denture base may promote the colonization of microorganisms, it is essential to know how the different types of denture bases prevent or encourage the adhesion of microorganisms. This study aimed to compare the microbial adhesion to the polished and fitting surfaces of thermoplastic nylon, thermoplastic acetal, and thermoplastic acrylic denture bases in Kennedy Class Ⅰ, partially edentulous patients. Materials and methods Thirteen patients were included in the study. The group consisted of eight males (61.54%) and five females (38.46%), with an age range of 41-50 years (mean age 46.1 years). Three types (groups) of removable partial dentures will be made for each patient using different thermoplastic denture base materials: thermoplastic nylon; thermoplastic acetal; and thermoplastic acrylic. The polished and fitting surfaces of the denture bases were swabbed after a one-month follow-up period. Microbial adhesion was evaluated by counting the microorganisms' colony-forming units (CFU) in the collected specimens. The data were collected and statistically analyzed. Results The study revealed no statistically significant difference in microbial adhesion to both polished and fitting surfaces between all types of studied thermoplastic denture base materials. However, the results showed that for the polished surface, the microbial adhesion median of thermoplastic acrylic denture base (40.5 CC x 102/ml) was higher than that of thermoplastic acetal (29.0 CC x 102/ml) and thermoplastic nylon (16.0 CC x 102/ml). Regarding the fitting surface, the microbial adhesion median of thermoplastic acrylic (51.0 CC x 102/ml) is higher than that of thermoplastic acetal (41.0 CC x 102/ml) and thermoplastic nylon (23.0 CC x 102/ml). Conclusion The thermoplastic nylon denture base materials showed less microbial adhesion among the studied thermoplastic materials, so it may be recommended to be used as a denture base material for individuals at high risk of denture stomatitis.

Bacterial sealing ability of calcium silicate-based sealer for endodontic surgery: an in-vitro study.

BACKGROUND: Apical surgery with standard retrograde maneuvers may be challenging in certain cases. Simplifying apical surgery to reduce operating time and streamline retrograde manipulation is an emerging need in clinical endodontics. AIM OF THE STUDY: The aim of the study was to compare the bacterial sealing ability of a calcium silicate-based sealer with the single cone technique combined with root end resection only, and calcium silicate-based sealer as a retrograde filling versus MTA retrofilling, and to analyze bacterial viability using confocal laser scanning microscope (CLSM). MATERIALS AND METHODS: In this in vitro experimental study, 50 extracted human maxillary incisor teeth were instrumented and randomly divided into five groups: three experimental groups, a positive control group, and a negative control group (n = 10/group). In the experimental groups, the roots were obturated using the single cone technique (SCT) and a calcium silicate-based sealer. In group 1, the roots were resected 3 mm from the apex with no further retrograde preparation or filling. In groups 2 and 3, the roots were resected, retroprepared, and retrofilled with either a calcium silicate-based sealer or MTA, respectively. Group 4 (positive control) was filled with a single gutta-percha cone without any sealer. In group 5 (negative control), the canals were left empty, and the roots were sealed with wax and nail varnish. A bacterial leakage model using Enterococcus faecalis was employed to assess the sealing ability over a 30-day period, checking for turbidity and analyzing colony forming units (CFUs) per milliliter. Five specimens from each group were examined using CLSM for bacterial viability. Data for the bacterial sealing ability were statistically analyzed using chi-squared and Kruskal-Wallis tests. RESULTS: The three experimental groups did not show significant differences in terms of bacterial leakage, or bacterial counts (CFUs) (P > 0.05). However, significant differences were observed when comparing the experimental groups to the positive control group. Notably, the calcium silicate-based sealer, when used as a retrofilling, yielded the best sealing ability. CLSM imaging revealed viable bacterial penetration in all the positive control group specimens while for the experimental groups, dead bacteria was the prominent feature seen. CONCLUSION: Within the limitations of this study, it could be concluded that the bacterial sealing ability of calcium silicate-based sealer with the single cone technique combined with root end resection only and calcium silicate-based sealer as a retrograde filling were comparable with MTA retrofilling during endodontic surgical procedures.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Retrieval of a Missing Translocated Intrauterine Contraceptive Device Using Combined Laparoscopic and Cystoscopic Techniques.

Background: Intrauterine contraceptive devices (IUCDs) are considered to be an effective way of preventing unwanted pregnancies. However, one significant complication associated with IUCDs is uterine perforation especially at the time of insertion and could reach the peritoneal cavity and the viscus of the adjacent organs. Intravesical migration is extremely rare. Case Presentation. We report a 41-year-old woman who was diagnosed with IUCD intravesical migration after she presented to our hospital complaining of persistent lower urinary tract symptoms. Laparoscopic removal was done after the failure of cystoscopic extraction. Conclusion: The IUCD must be monitored continuously by the gynaecologist, and suspicions of intravesical migration must be considered in those presenting with persistent, unexplained lower urinary tract symptoms.

Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules.

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

Mid-infrared Imaging Using Strain-Relaxed Ge1-xSnx Alloys Grown on 20 nm Ge Nanowires.

Germanium-tin (Ge1-xSnx) semiconductors are a front-runner platform for compact mid-infrared devices due to their tunable narrow bandgap and compatibility with silicon processing. However, their large lattice parameter has been a major hurdle, limiting the quality of epitaxial layers grown on silicon or germanium substrates. Herein, we demonstrate that 20 nm Ge nanowires (NWs) act as effective compliant substrates to grow extended defect-free Ge1-xSnx alloys with a composition uniformity over several micrometers along the NW growth axis without significant buildup of the compressive strain. Ge/Ge1-xSnx core/shell NWs with Sn content spanning the 6-18 at. % range are achieved and processed into photoconductors exhibiting a high signal-to-noise ratio at room temperature with a cutoff wavelength in the 2.0-3.9 µm range. The processed NW devices are integrated in an uncooled imaging setup enabling the acquisition of high-quality images under both broadband and laser illuminations at 1550 and 2330 nm without the lock-in amplifier technique.

The Use of Thoracic Segmental Spinal Anaesthesia for Thoracoscopic Diaphragmatic Hernia Repair in an Adult With Cardiac Compromise.

Morgagni hernias are uncommon diaphragmatic defects and are commonly found incidentally as a congenital defect. Acquired Morgagni hernias have been documented in the pediatric population, making them extremely uncommon. Thoracic segmental spinal anesthesia (TSSA) may be used as a successful substitute for general anesthesia, especially in cardiovascularly compromised patients like our patient who had heart failure with reduced ejection fraction (HFrEF), and this is one of the very few documented cases of acquired Morgagni hernia laparoscopic repair surgery done by this anesthesia method. An 80-year-old woman presented with a complaint of left lower chest and left upper quadrant pain. Acute coronary artery syndrome was ruled out. She underwent a coronary artery bypass graft in 2009, complicated two months later by mediastinitis, which is believed to be the cause of the acquired diaphragmatic defect in our patient. Chest and abdominal CT showed a large anterior Morgagni-type diaphragmatic hernia, in which the left hemithorax and anterior mediastinum were both occupied by a herniated transverse colon. Under regional anesthesia, which was done by injecting anesthesia in the spinal space between thoracic spinal vertebrae T8 and T9 and second injections in the epidural space at the level between thoracic epidural T9 and T10, which is neuraxial anesthesia. The repair of the diaphragmatic hernia was done by suturing the mesh into the proper position. We report the first known case of laparoscopic repair of a Morgagni hernia in an adult patient with HFrEF and other comorbidities.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.