The expression of both constitutive and inducible forms of nitric oxide synthase (NOS) was investigated by immunohistochemical staining of formalin-fixed paraffin-embedded sections in normal and Listeria monocytogenes-infected brains of goats. In normal control goats, a small number of neurons showed immunoreactivity of both iNOS and nNOS, and the number of iNOS-positive neurons was higher than the number of nNOS-positive neurons. In natural listeriosis, listeria antigens were easily immunostained in the inflammatory cells of microabscesses. In this lesion, the immunoreactivity of iNOS in neurons was more intense than the control, but nNOS was not. In microabscesses, nNOS was weakly visualized in macrophages and neutrophils, while iNOS was expressed in macrophages, but not in neutrophils. These findings suggest that normal caprine brain cells, including neurons, constitutively express iNOS and nNOS, and the expressions of these molecules is increased in Listeria monocytogenes infections. Furthermore, inflammatory cells, including macrophages, expressing both nNOS and iNOS may play important roles in the pathogenesis of bacterial meningoencephalitis in goat.
Animals ; Brain/cytology/*enzymology ; Glial Fibrillary Acidic Protein/analysis ; Goat Diseases/*enzymology ; Goats ; Immunohistochemistry ; Listeria Infections/enzymology/*veterinary ; Neurons/*enzymology ; Nitric Oxide Synthase/*analysis ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II

OBJECTIVE: The aim of the study is to determine the efficacy of indocyanine green (ICG) videoangiography for confirmation of vascular anastomosis patency in both extracranial-intracranial and intracranial-intracranial bypasses. METHODS: Intraoperative ICG videoangiography was used as a surgical adjunct for 56 bypasses in 47 patients to assay the patency of intracranial vascular anastomosis. These patients underwent a bypass for cerebral ischemia in 31 instances and as an adjunct to intracranial aneurysm surgery in 25. After completion of the bypass, ICG was administered to assess the patency of the graft. The findings on ICG videoangiography were then compared to intraoperative and/or postoperative imaging. RESULTS: ICG provided an excellent visualization of all cerebral arteries and grafts at the time of surgery. Four grafts were determined to be suboptimal and were revised at the time of surgery. Findings on ICG videoangiography correlated with intraoperative and/or postoperative imaging. CONCLUSION: ICG videoangiography is rapid, effective, and reliable in determining the intraoperative patency of bypass grafts. It provides intraoperative information allowing revision to reduce the incidence of technical errors that may lead to early graft thrombosis.
Brain Ischemia ; Cerebral Arteries ; Humans ; Incidence ; Indocyanine Green ; Intracranial Aneurysm ; Thrombosis ; Transplants

OBJECTIVE: Obesity has been shown to be associated with adverse outcomes in viral infections such as influenza, but previous studies on coronavirus disease 2019 (COVID-19) had mixed results. The aim of this systematic review is to investigate the relationship between COVID-19 and obesity. METHODS: We performed a systematic review and meta-analysis. A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL, OpenGrey and preprint servers medRxiv and bioRxiv was performed, with no restriction on language or date of publication. Primary outcomes of this study were intensive care unit (ICU) admission or critical disease, severe disease and mortality. Secondary outcome was a positive COVID-19 test. Meta-analysis was performed using OpenMeta-Analyst software, and heterogeneity was tested using Cochran's Q test and I2 statistic. The study protocol was registered on PROSPERO (CRD42020184953). RESULTS: A total of 1,493 articles were identified and 61 studies on 270,241 patients were included. The pooled prevalence of obesity was 27.6% (95% confidence interval [CI] 22.0-33.2) in hospitalised patients. Obesity was not significantly associated with increased ICU admission or critical illness (odds ratio [OR] 1.25, 95% CI 0.99-1.58, CONCLUSION Obesity increased the risk of severe disease, mortality and infection with COVID-19. Higher body mass index was associated with ICU admission and critical disease. Patients who are obese may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and infected patients should be monitored closely for adverse outcomes.
Body Mass Index ; COVID-19/therapy* ; Critical Care ; Critical Illness ; Global Health ; Hospitalization ; Humans ; Obesity/complications* ; Prognosis ; Risk Factors ; Severity of Illness Index

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin condition that can affect any area with apocrine sweat glands and has the potential to involve multiple sites concurrently. Commonly affected sites include the axilla, groin, perineum and perianal areas. In this study we performed a literature review on the surgical methods for HS and describe an innovative technique for reconstructing axilla HS using an inner-arm transposition flap. METHODS: We reviewed all cases (5 cases from 4 patients) of transposition flap reconstruction performed by the senior author at a single London tertiary hospital from 2008–2013. Patient related outcome measures were collected using the Derriford appearance scale (DAS 24) and a study specific questionnaire. RESULTS: All patients were satisfied with their final result. One out of five cases had a complication but did not result in flap failure. There is no disease recurrence to date. DAS 24 scores collected demonstrated acceptable postoperative distress that did not deviate far from the norm tables while study specific questionnaire reveal desirable outcomes. CONCLUSIONS: We have managed to achieve our aim through the use of the innovative inner-arm transposition flap. Our study hopes to provide an additional technique for axillary reconstruction. This technique offers the effective concealment of scars with the benefit of tightening of the arm tissue producing ‘brachioplasty like’ effects. All things considered it would be reasonable to conclude the innovative flap technique is a reliable, effective, and simple method that results in multiple benefits.
Arm ; Axilla ; Cicatrix ; Groin ; Hidradenitis Suppurativa* ; Hidradenitis* ; Hope ; Humans ; Methods ; Outcome Assessment (Health Care) ; Perineum ; Recurrence ; Skin ; Surgical Flaps ; Sweat Glands ; Tertiary Care Centers

BACKGROUND: To compare the stability of fixed- versus variable-angle locking constructs for the comminuted distal humerus fracture (AO/OTA 13-A3). METHODS: Eight pairs of complete humeri harvested from eight fresh frozen cadavers were used for the study. We fixed the intact humeri using 2.7-mm/3.5-mm locking VA-LCP stainless steel distal humerus posterolateral (nine-hole) and medial (seven-hole) plates. An oscillating saw was used to cut a 1-cm gap above the olecranon fossa. The specimens were loaded in axial mode with the rate of 1 mm per 10 seconds to failure, and stress-strain curves were compared in each pair. The mode of failure was recorded as well as the load needed for 2- and 4-mm displacement at the lateral end of the gap. RESULTS: The stiffness of the constructs, based on the slope of the stress-strain curve, did not show any difference between the fixed- versus variable-angle constructs. Likewise, there was no difference between the force needed for 2- or 4-mm displacement at the lateral gap between the fixed- and variable-angle constructs. The mode of failure was bending of both plates in all specimens and screw pull-out in four specimen pairs in addition to the plate bending. CONCLUSIONS: Our results did not show any difference in the biomechanical stability of the fixed- versus variable-angle constructs. There was not any screw breakage or failure of the plate-screw interface.
Bone Screws ; Cadaver ; Fracture Fixation ; Fractures, Comminuted ; Humerus ; Olecranon Process ; Stainless Steel

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.

Objective:To investigate the short term clinical efficacy of intra-gastric balloon (IGB) on obesity patients with different body mass index (BMI).Methods:The retrospective and descriptive study was conducted. The clinical data of 62 obesity patients with different BMI who were admitted to three medical centers, including 56 cases in the Hurstville Private Hospital, 4 cases in the St George Private Hospital of University of New South Wales and 2 cases in the East Sydney Private Hospital, from January 2017 to December 2021 were collected. There were 15 males and 47 females, aged 45.1(range, 18.0 to 67.0)years, with the BMI of 35.1(range, 27.8 to 48.4)kg/m 2. Of the 62 patients, there were 33 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 29 cases with BMI≥35 kg/m 2. Observation indicators: (1) first operation and postoperative complications; (2) follow-up after first IGB; (3) recurrent IGB and postoperative complications; (4) follow up after recurrent IGB. Follow-up was conducted using outpatient examinations to detect postoperative complications and weight loss effects. Patients were followed up at postoperative 1, 3, 6 month. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers. Results:(1) First opera-tion and postoperative complications. All 62 obesity patients underwent the first IGB successfully. Of the 62 patients, 45 cases had postoperative complications, including 38 cases with gastroesophageal reflux, 12 cases with dysphagia or burping, 9 cases with epigastric pain and 4 cases with nausea. One patient may have multiple complications. Cases with above complications in the 33 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 29 cases with BMI≥35 kg/m 2 were 21, 8, 7, 2 and 17, 4, 2, 2, respectively. (2) Follow-up after first IGB. Of the 62 obesity patients, there were 52, 46 and 38 cases completing followed up at postoperative 1, 3 and 6 month, respectively, including 30, 25,20 cases in patients with 27 kg/m 2≤BMI<35 kg/m 2 and 22, 21, 18 cases in patients with BMI≥35 kg/m 2. Of the 62 obesity patients, there were 15 cases requiring early balloon extraction due to intractable symptoms, inclu-ding 7 cases with ongoing dysphagia or burping, 6 cases with complaining of ineffective weight loss, 1 case with acute right-sided abdominal pain and 1 case with a serendipitous discovery of pregnant. The cumulative weight loss of the 30 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 22 cases with BMI≥35 kg/m 2 at postoperative 1 month was (4.8±3.0)kg and (6.6±2.8)kg, respectively. The above indicator was (6.7±4.4)kg and (10.6±4.8)kg at postoperative 3 month for the 25 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 21 cases with BMI≥35 kg/m 2, and (8.5±4.8)kg and (9.8±3.9)kg at postoperative 6 month for the 20 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 18 cases with BMI≥35 kg/m 2. The percentage of excess weight loss was 53%±26% and 29%±15% at postoperative 6 month and the percentage of total weight loss was 14%±5% and 10%±5% at postoperative 6 month for the 20 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 18 cases with BMI≥35 kg/m 2, respectively. (3) Recurrent IGB and postoperative complications. Of the 38 cases completing the postoperative 6 month followed up after the first IGB, 9 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 7 cases with BMI≥35 kg/m 2 choosing a second IGB immediately after the removal of the first balloon. Cases with postoperative compli-cations, including gastroesophageal reflux, dysphagia or burping, epigastric pain, nausea were 4, 3, 0, 0 in patients with 27 kg/m 2≤BMI<35 kg/m 2 and 4, 0, 2, 1 in patients with BMI≥35 kg/m 2. (4) Follow up after recurrent IGB. All the 16 patients who chosen a second IGB completed the postoperative 6 month followed up, with the cumulative weight loss of (8.8±8.5)kg and (18.9±9.7)kg and the percentage of excess weight loss of 44%±38% and 41%±15% in the 9 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 7 cases with BMI≥35 kg/m 2, respectively. Conclusions:IGB can achieve a good short-term weight loss effects in obesity patients with BMI≥27 kg/m 2. Gastroesophageal reflux, dysphagia or burping, epigastric pain and nausea are common postoperative complications.

Objective:To investigate whether polyethylene glycol hydrogel films (PHFs) can be used as a carrier for the expansion of corneal epithelial cells (CECs) in vitro and whether PHFs can be used in the treatment of limbal stem cell deficiency (LSCD). Methods:Sebacoyl chloride, dihydroxyl PCL and glycerol ethoxylate were used to synthesize PHFs.The thickness, transmittance and mechanical tensile properties of PHFs were measured.Four clean-grade New Zealand white rabbits were selected to culture primary limbal epithelial cells.The expression of keratin marker AE1/AE3 and stem cell marker p63 in the cultured cells were observed under a fluorescence microscope.The cells were divided into negative control group cultured with common cell culture solution, positive control group cultured with cell culture solution containing 100 μmol/L H 2O 2, and PHFs+ CECs group lined with PHFs cultured with common cell culture solution for 24 hours.The proliferation and apoptosis of cells in the three groups were observed by MTT and TUNEL staining, respectively.Fifteen clean-grade New Zealand white rabbits were divided into control group, PHFs group and PHFs+ CECs group by random number table method, with 5 rabbits in each group.LSCD model was constructed in the three groups.The control group was not given any treatment after modeling.In PHFs group, empty PHFs were placed on the corneal surface of rabbits.In PHFs+ CECs group, tissue-engineered grafts constructed with CECs after passage implanted on PHFs were placed on the corneal surface of rabbits.The corneal defect area of rabbits was detected and scored by fluorescein sodium staining.The histological characteristics of rabbits corneal epithelium was observed by hematoxylin-eosin staining.The use and care of animals complied with Guide for the Care and Use of Laboratory Animals by the U. S.National Research Council.The experimental protocol was approved by the Research and Clinical Trial Ethics Committee of The First Affiliated Hospital of Harbin Medical University (No.2021006). Results:The synthetic PHFs were with a thickness ≤150 μm, a tensile strength about 6 MPa, and a transmittance over than 99% in the range of 400-700 nm.Most of the cells from primary culture of limbal tissue were positive for AE1/AE3 and p63.MTT test results showed that the A490 value of PHFs+ CECs group, negative control group and positive control group was 0.59±0.01, 0.65±0.07 and 0.06±0.04, respectively, showing a statistically significant overall difference ( F=12.25, P<0.05). The A490 values of PHFs+ CECs group and negative control group were significantly higher than that of positive control group, and the differences were statistically significant (both at P<0.05). TUNEL test results showed that there was a significant difference in the TUNEL-positive cell rate among the three groups ( F=13.45, P<0.05), and the rates of TUNEL-positive cells in PHFs+ CECs group and negative control group were significantly lower than that in positive control group (both at P<0.05). Fluorescein sodium staining results showed that with the extension of postoperative period, the corneal fluorescein sodium staining score of the three groups decreased, which decreased successively in control group, PHFs group and PHFs+ CECs group.Hematoxylin-eosin staining showed fewer irregularly shaped corneal epithelial cells in the control group, and sparse single layer of corneal epithelial cells in some areas of the PHFs group.In PHFs+ CECs group, the corneal epithelium coverage was the largest, and the cell layers increased to 3-5, and the cells were with regular morphology and in close arrangement. Conclusions:PHFs have enough toughness, high transmittance and can expand corneal epithelium in vitro.PHFs are suitable for corneal epithelial transplantation and can promote the repair of corneal epithelium in rabbit model of LSCD.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods: Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate and regulate cardiac rhythm and rate. It has been suggested that, unlike the HCN1 and HCN2 channels, the slower HCN4 channel may not exhibit voltage-dependent hysteresis. We studied the electrophysiological properties of human HCN4 (hHCN4) channels and its modulation by cAMP to determine whether hHCN4 exhibits hysteresis, by using single-cell patch-clamp in HEK293 cells stably transfected with hHCN4. Quantitative real-time RT-PCR was also used to determine levels of expression of HCNs in human cardiac tissue. Voltage-clamp analysis revealed that hHCN4 current (I(h)) activation shifted in the depolarizing direction with more hyperpolarized holding potentials. Triangular ramp and action potential clamp protocols also revealed hHCN4 hysteresis. cAMP enhanced I(h) and shifted activation in the depolarizing direction, thus modifying the intrinsic hHCN4 hysteresis behavior. Quantitative PCR analysis of human sinoatrial node (SAN) tissue showed that HCN4 accounts for 75% of the HCNs in human SAN while HCN1 (21%), HCN2 (3%), and HCN3 (0.7%) constitute the remainder. Our data suggest that HCN4 is the predominant HCN subtype in the human SAN and that I(h) exhibits voltage-dependent hysteresis behavior that can be modified by cAMP. Therefore, hHCN4 hysteresis potentially plays a crucial role in human SAN pacemaking activity.
Biological Clocks ; physiology ; Cyclic AMP ; physiology ; Cyclic Nucleotide-Gated Cation Channels ; physiology ; Electrophysiological Phenomena ; HEK293 Cells ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Muscle Proteins ; physiology ; Patch-Clamp Techniques ; Potassium Channels ; Sinoatrial Node ; physiology ; Transfection