Group 2C Research Articles

Effects of In Vivo / In Vitro Melatonin Application on the Duodenum in Rats with Experimental Hyperthyroidism

The aim of this study was to investigate the effects of melatonin on the intestinal motility of hyperthyroidism rats. Therefore, we determined in vivo and in vitro effects of melatonin on duodenal tissue in experimental hyperthyroid rats. 34 Wistar-Albino male rats were fed with physiological conditions, and then euthanized by cervical dislocation. The experimental animals, Group 1: Control group (n=5), Group 1B: Melatonin group in vitro (n=5), Group 1C: Melatonin group in vivo (n=6), Group 2: 2A: Hypertension group (n=6), 2B: Group 2: Hyperthyroidi sm in vitro melatonin group (n=6), 2C: Hyperthyroidism in vivo melatonin group (n=6). Acetylcholine (ACh, 10-7, 10-6, 10-5, 10-4, 10-3, 10-2 M), potassium chloride (KCl, 20, 40, 60, 80, 100 mM) at the end of the incubation period different doses were given to the bathing environment. In in vitro melatonin groups, the determined submaximal doses (ACh 10-4 M, KCl 60 mM) and melatonin at different doses (Mel 10-10, 10-9, 10-8, 10-7, 10-6, 10-5 and 10-4 M) were applied. It was determined that the contraction responses of the isolated duodenal tissues induced by KCl and ACh increased significantly (p

Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study.

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease in infants and children with potential for fatal complications such as encephalitis and acute flaccid myelitis. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine adjuvanted with aluminum phosphate, in children from the age of 2 months to <6 years, for up to 5 years after the first immunization. A total of 227 participants between 2 months and <6 years of age who had previously received either EV71vac or placebo in the phase two clinical study were enrolled. Subjects were divided into age groups: 2 years to <6 years (Group 2b), 6 months to <2 years (Group 2c), and 2 months to <6 months (Group 2d). At Year 5, the neutralizing antibody titers against the B4 subgenotype remained high at 621.38 to 978.20, 841.40 to 1159.93, and 477.71 to 745.07 for Groups 2b, 2c, and 2d, respectively. Cross-neutralizing titers at Year 5 remained high against B5 and C4a subgenotypes, respectively. No long-term safety issues were reported. Our study provides novel insights into the long-term immunity conferred by EV71vac in children aged from two months to six years, particularly in those who received EV71vac between two and six months of age.

P-281 Surgery and IVF for diagnosed ovarian endometriosis and deep infiltrative endometriosis

Abstract Study question To evaluate the effectiveness of surgical treatment of endometrioid cysts and deep infiltrative endometriosis before an IVF program Summary answer Laparoscopic excision of deep infiltrative endometriosis has a positive effect on the reproductive function of women What is known already One of the most severe and aggressive manifestations of endometriosis is deep infiltrative endometriosis. Endometriosis is a socially significant disease that reduces a woman’s quality of life and affects reproductive health. Women with endometriosis often experience severe menstrual and non-menstrual pain affecting the lower abdomen, pelvis or lumbosacral region, profound dyspareunia, dyschezia and dysuria (Uimari et al., 2021) and infertility in 30–50% of cases (Prescott et al.., 2016). Patients with endometriosis suffer from chronic fatigue (Ramin-Wright et al., 2018) and have a higher risk of mental health problems (56.4%) than patients without endometriosis (43.6%) (Pope et al., 2015) Study design, size, duration The our institute is conducting a controlled, non-randomized, retro- and prospective study on genital endometriosis. The study period is from 2012 to the present. Participants/materials, setting, methods The study included 450 women with deep infiltrating endometriosis in combination with infertility All patients were divided into 4 groups Group 1 – 128 patients with deep infiltrative endometriosis, sent for IVF without surgery Group 2 – 297 patients with deep infiltrative endometriosis, initially referred for surgery Group 2a – 156 patients with ovarian cysts, sent for preliminary collection of eggs before surgery Group 2c – 141 patients with ovarian cysts, referred for surgery without prior egg retrieval Main results and the role of chance In group 1, the number of pregnancies occurred was 65.6% (84 women), in group 2a - 71.7% (112 women), in group 2 - 53.9% (76 women). Pregnancy occurred spontaneously in 18 (4.2%) women from group 2 after surgery. In group 2, four women, after three unsuccessful attempts at in vitro fertilization, became pregnant after using donor eggs - the results were excluded from the final pregnancy calculations. In terms of pregnancy, IVF with preliminary surgery (Me: 2.10; Q1-Q-3:0) had a statistically significant advantage compared to IVF without surgery (Me: 5.00; Q1-Q-3:0), and IVF with surgery without egg retrieval (Me:3.0; Q1-Q-3:0). The lowest statistically significant pregnancy rate was recorded during laparoscopic surgery without prior egg retrieval (Me: 6.95; Q1-Q-3:1). When performing a post-hoc analysis, a statistically significant shorter pregnancy time was also found when performing IVF with preliminary laparoscopy and egg freezing: group 1 (M: 126.25; SD111.1), group 2a (M: 79.97; SD: 19.785 ), group 2c (M: 130.50; SD: 82.149) (p = 0.000). During the period of observation of women for twelve years after surgery, 93% of patients noted an improvement in the quality of life and 63.7% of women on average achieved reproductive function after the IVF program for endometriosis. Limitations, reasons for caution no restrictions Wider implications of the findings The results of the IVF program for deep infiltrative endometriosis are statistically higher after surgery, but with preliminary cryopreservation of oocytes. The question of radical resection of the rectum in comparison with shaving when planning an IVF program remains open, which forms the planning of further research in this area. Trial registration number not applicable

TOWARDS UNDERSTANDING MÜLLER-WEISS DISEASE: A UNIVERSAL PLATFORM

BackgroundThe only existing classification of Müller-Weiss Disease (MWD), based solely on Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management.MethodsNavicular compression, medial extrusion, Kite's angle and metatarsal lengths were measured on all radiographs of 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded.ResultsWe identified three distinct groups. Group 1 comprises 11 “early-onset” MWD feet, aged 9 to 29 years. These had the greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had a lateral navicular fracture. None has required surgery to date. Only 1 has moderate talonavicular joint (TNJ) degeneration.Group 2 comprises 23 “Müller-Weissoid” feet with radiologically normal navicular in their fifties and developing MWD, on average, 4.5 years later. These had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 “late-onset” MWD, presenting in the sixth decade, is subdivided into 3 sub-groups. Only TNJ is involved in group 3A (16). Group 3B denotes affection of TNJ more than NCJ (20). In group 3C “reverse Müller-Weiss disease”, which affects NCJ more than TNJ (25), second metatarsal overlength is highest of all groups. No difference in age, compression, extrusion and Kite's angle exists among the 3 subgroups. No fracture occurred in group 3A compared to 65% and 32% in groups 3B and 3C, respectively.ConclusionsWith a need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatment modalities, operative or nonoperative. We theorize pathogenetic pathways in the different groups and propose systematic surgical approaches for each category.

Genetic Findings in Short Turkish Children Born to Consanguineous Parents.

The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented. This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height &lt;-3.5 standard deviation score [SDS]) and microcephaly (head circumference &lt;-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c). In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively. Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.

Differential Contribution of Hydrogen Metabolism to Proteus mirabilis Fitness during Single-Species and Polymicrobial Catheterized Urinary Tract Infection.

Proteus mirabilis is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for P. mirabilis CAUTI: a Hyb-type Group 1c H2-uptake hydrogenase and a Hyf-type Group 4a H2-producing hydrogenase. In this study, we disrupted one gene of each system (hyfE and hybC) and also generated a double mutant to examine the contribution of flexible H2 metabolism to P. mirabilis growth and fitness in vitro and during experimental CAUTI. Since P. mirabilis is typically present as part of a polymicrobial community in the urinary tract, we also examined the impact of two common co-colonization partners, Providencia stuartii and Enterococcus faecalis, on the expression and contribution of each hydrogenase to fitness. Our data demonstrate that neither system alone is critical for P. mirabilis growth in vitro or fitness during experimental CAUTI. However, perturbation of flexible H2 metabolism in the ∆hybC∆hyfE double mutant decreased P. mirabilis fitness in vitro and during infection. The Hyf system alone contributed to the generation of proton motive force and swarming motility, but only during anaerobic conditions. Unexpectedly, both systems contributed to benzyl viologen reduction in TYET medium, and disruption of either system increased expression of the other. We further demonstrate that polymicrobial interactions with P. stuartii and E. faecalis alter the expression of Hyb and Hyf in vitro as well as the contribution of each system to P. mirabilis fitness during CAUTI.

Photodynamic therapy in the treatment of vulvar lichen sclerosus et atrophicus

Lichen sclerosus (LS) is a chronic inflammatory disease that is 6–10 times more common in women than in men. LS affects between 1 in 1,000 and 1 in 300 people in the general population, but the exact prevalence is unknown since the disease is often asymptomatic. Objective: to evaluate the effectiveness of PDT in patients with LS in comparison with standard therapy methods. Material and methods: The study included 45 patients diagnosed with LS aged from 45 to 72 years (median age was 59 years). Depending on the therapy performed, the groups were divided into subgroups: Group 1A — patients with LS who were prescribed therapy with external glucocorticoids, Group 1B — patients with LS who were prescribed photodynamic therapy, Group 1C — patients with LS who were prescribed combined treatment: external glucocorticoids + PDT. Results: The study developed a special visual analogue scale to assess the objective condition of the vulva. VAS included the following parameters: pigmentation, skin pattern, turgor (skin fold straightening time), presence of cracks or erosions, and moisture. According to the data obtained, a complex treatment method using photodynamic therapy in patients with vulvar lichen sclerosus et atrophicus causes a higher effect than drug therapy and mono-PDT, which is confirmed by the dynamics of the total VAS index: 50.8 % compared with 28.2 % and 35.1 % in the comparison groups, respectively, therefore, it can be recommended for use in practical healthcare.

A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus.

The repeated emergence of zoonotic human betacoronaviruses (β-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)-related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/li/GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/Mpro protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV-neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo-electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.

Refractive change in pediatric patients with intermittent exotropia

To determine the relationship between intermittent exotropia (IXT) and refractive change and the effects of the methods applied in IXT follow-up on refractive change. The medical records of 228 patients with IXT (group 1) and 110 patients without strabismus (group 2) who were followed between 2008 and 2022 were analyzed retrospectively. Group 1 was divided into three subgroups: overminus correction (group 1A), patients who underwent surgery (group 1B), and patients who were observed (group 1C). Annual myopic progression was -0.21 ± 0.32 D (range, -1.26 to +1.92) in group 1 and -0.07 ± 0.30 D (range, -1.13 to +1.00) in group 2 (P < 0.001). Annual myopic progression was -0.26 ± 0.29 D (range, -1.26 D to +0.12 D) in group 1A, -0.25 ± 0.35 D (range, -1.15 D to +0.25 D) in group 1B, and -0.19 ± 0.33 D (range, -1.12 D to +1.92 D) in group 1C. There was no difference in annual myopic progression between the subgroups (P = 0.670). The annual change in myopic refraction between each of the group 1 subgroups and group 2 was statistically significantly different (P < 0.001, P = 0.023, P< 0.001, resp.). Myopia progression was significantly greater in children with IXT than in the normal population. Myopia progression did not vary with exotropia treatment.

Do bilateral procedures further increase the complications for autologous breast reconstruction in obese patients?

Obesity is known to be associated with high complication rates. The aim of this study was to evaluate the effect of bilateral procedures on complication rates in obese patients undergoing autologous breast reconstruction with deep inferior epigastric perforator flaps. Medical records of patients undergoing autologous breast reconstruction between January 2017 and December 2019 were retrospectively reviewed. Patients were divided into two groups according to their body mass index (BMI): Group 1 (BMI > 30) and Group 2 (BMI < 30). Group 1 was further divided into 3 subgroups: Group 1a (bilateral reconstruction), Group 1b (unilateral reconstruction), and Group 1c (unilateral reconstruction and contralateral symmetrization). Outcomes and complication rates were compared between groups. Ninety-one patients (with 119 free flaps) were followed up between 6 and 12months. Length of hospital stay, smoking rates, and age were similar in all groups. Group 1 had significantly more rates of wound dehiscence (p = 0.024), mastectomy skin flap necrosis (p = 0.019), and re-operation (p = 0.033). The operation time was significantly higher in group 1 (p = 0.003). There was no significant difference between group 1 and group 2 in terms of hematoma-seroma formation, flap loss, and pulmonary thromboembolism rates. When obese subgroups were compared, no significant difference was observed in terms of complications. In our series, microvascular breast reconstruction was associated with more complication rates in obese patients. However, bilateral procedures in the obese patient group did not significantly increase risk of complications as compared to unilateral procedures. By taking appropriate measures bilateral procedures can be performed in obese patients without additional risks.

Survival Outcomes of Patients with Esophageal Cancer Who Did Not Proceed to Surgery after Neoadjuvant Treatment.

This retrospective study examined outcomes in esophageal squamous cell carcinoma (ESCC) patients who did not undergo surgical resection after neoadjuvant chemoradiotherapy (nCRT). Patients receiving nCRT between 2012 and 2020 were divided into two groups: group 1 (scheduled surgery) and group 2 (no surgery). Group 2 was further categorized into subgroups based on reasons for not proceeding to surgery: group 2a (disease progression), group 2b (poor general conditions), and group 2c (patient refusal). Overall survival (OS) was the primary outcome. Group 1 comprised 145 patients, while subgroups 2a, 2b, and 2c comprised 24, 16, and 31 patients, respectively. The 3-year OS rate was significantly lower in group 2 compared with group 1 (34% versus 56%, p < 0.001). A subgroup analysis showed varying 3-year OS rates: 13% for group 2a, 25% for group 2b, and 58% for group 2c (p < 0.001). Propensity score matching for group 2c and group 1 revealed no significant difference in 3-year OS rates (p = 0.91). One-third of ESCC patients receiving nCRT did not undergo surgical resection. Overall survival in this group was generally poorer, except for those who refused surgery (group 2c).

Rationally designed novel phenazine based chemosensor with real time Hg2+ sensing application

Phenazine derivatives have been explored in the selective detection of ions due to their binding ability with analytes. In this context, C-6 sulfenylated benzo[a]phenazine-5-ols (3a-d)have been synthesied and explored in sensing application. Initially, the molecules were designed by utilizing benzo[a]phenazin-5-ol as a core structure variably substituted with electronically diverse aryl thiols to investigate the substituent effect on their electrostatic properties. The ground state geometry of all the designed molecules was optimized with DFT using B3LYP/6-311G+(d,p) level of theory. Energy gap between FMOs was observed to be minimum and maximum for electron rich and deficient frameworks, respectively. The LUMO electron density in all the designed molecules except for compound bearing nitro group (3c) lies on the phenazine unit. This exceptional behavior enthusiased us to explore their photophysical properties. The compounds were synthesized and characterized using FT-IR, NMR and mass spectrometric techniques. In an attempt to examine their spectral behavior in different solvents, their absorption and emission spectra were recorded. The compounds exhibited absorptions maxima ranging between 475-514 nm, which shifted to longer wavelength while changing solvent polarity from CHCl3 to DMSO thus depicting positive solvatochromism. Similarly, the emission maxima was observed in a range of 570–685 nm with a maximum stokes shift of 6454 cm−1 for 3c. The compound 3c was further explored in the sensing application using DMSO:Water (60:40, v/v) mixture. A blue shift of 30 nm with nearly 7 fold increase in the emission intensity was observed upon addition of Hg2+ into 3c solution. Moreover, LOD of 21.9 nM and binding stoichiometry of 2:1 as determined by Benesi–Hildebrand and Job's plot establish the robust response of developed probe towards Hg2+ ion. The mechanism of complex formation was predicted by 1H NMR titration and DFT studies. Finally, the developed probe has been successfully utilized for sensing Hg2+ in real water samples.

Syntheses and Structures of Arenethiolato Cobalt(II) Complexes Containing Acylamino Groups: Steric Effects of Bulky Ligands on Coordination and Geometry.

Bulky thiolato ligands have been developed for creating biomimetic model complexes of active sites in metalloenzymes. Herein, we report a series of di-ortho-substituted arenethiolato ligands containing bulky acylamino groups (RCONH; R = t-Bu-, (4-t-BuC6H4)3C-,{3,5-(Me2CH)2C6H3}3C-, and {3,5-(Me3Si)2C6H3}3C-) that were developed for biomimetics. Bulky hydrophobic substituents generate a hydrophobic space around the coordinating sulfur atom through the NHCO bond. This steric environment induces the formation of low-coordinate mononuclear thiolato Co(II) complexes. The well-positioned NHCO moieties in the hydrophobic space coordinate to the vacant sites of the cobalt center with different coordination modes, viz., the S,O-chelate of the carbonyl C═O or the S,N-chelate of the acylamido CON-. The solid (crystalline) and solution structures of the complexes were investigated in detail using single-crystal X-ray crystallography, 1H NMR, and absorption spectroscopic analyses. The spontaneous deprotonation of NHCO, which is commonly observed in metalloenzymes but requires a strong base in artificial systems, was simulated by forming a hydrophobic space in the ligand. This new ligand design strategy is advantageous for creating model complexes that have never been constructed artificially.

Investigation of the effects of inflammatory and metabolic factors on fracture union in head trauma and long bone fractures

Background/Aim: Fractures are the most common form of trauma in current orthopedic practice. Although studies have shed light on the relationship between the factors affecting the healing process after fracture, this process is still not fully understood. In this study, we aimed to investigate the changes in serum biomediator levels and fracture healing in different trauma patterns, such as head trauma (HT), long bone fracture (LBF), a combination of HT + LBF injury (CI), and in different time points of the healing period.&#x0D; Methods: Forty Wistar rats were included in the study and divided into five groups. Group 1, the donor group, included rats with HT; Group 2 included rats with LBFs who were administered the serum taken from rats in Group 1; Group 3 included the rats with isolated LBFs; and Group 4 the rats with CI. Group 5 comprised the control rats. An experimental closed HT and fracture model was applied to rats. The rats in Groups 2, 3 and 4 were sacrificed on the 10th, 20th, and 30th days. The biomediator levels in the serum taken after sacrification were studied, while closed femoral fracture models were examined radiologically.&#x0D; Results: Statistically significant differences were found among the groups regarding radiological scores on the 10th, 20th, and 30th days. On Day 10, Group 2a had significantly higher scores than Group 3a (P=0.03), and Group 3a had lower scores than Group 4a (P=0.01). On Day 20, Group 2b had significantly higher scores than Group 3b (P=0.004) but lower than Group 4b (P=0.03). On Day 30, Group 2c had significantly higher scores than Group 3c but lower than Group 4c (P=0.001). The mean Ca, TGF beta 1, beta-catenin, IL-10, IL-17A, TNF alpha, CRP, Wnt-16, ALP, GH, PTH, IL-1 beta, IL-6, and IL-22 levels were significantly different among the groups (P&lt;0.05). No significant difference was observed in the biomediator levels among the groups at different time points of the healing period.&#x0D; Conclusion: We concluded that inflammatory cytokines (IL-1 beta, IL-6, IL-17A, IL-17F, IL-23, and TNF alpha) were elevated in the early period in individuals with isolated head trauma and that this effect could be transferred to other individuals by serum transfer. On the other hand, the negative relationship between the IL-10 level, which is a negative modulator in fracture union, and callus thickness was significant. Our study contributes by providing a molecular description of the positive union effect transferred between individuals by serum. We believe our findings will play a significant role in developing new therapeutic agents for fracture healing.

Influence of non-alcoholic steatohepatitis on the renal functional status in patients with type 2 diabetes and diabetic kidney disease

Background. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) are considered the most common liver pathologies, which in developed countries is observed in 20–30% of the adult population. Patients with diabetes mellitus (DM) often develop non-specific kidney lesions such as asymptomatic bacteriuria, pyelonephritis, kidney carbuncle, kidney abscess, kidney tuberculosis, necrotizing papillitis, or papillary necrosis, which significantly complicate the course of diabetic nephropathy (DN). DN accounts for 40% of complications in type 1 DM and 5–15% among patients with type 2 DM. The purpose of the study is to clarify the impact of non-alcoholic steatohepatitis on the renal functional status in patients with type 2 diabetes and diabetic kidney disease (DКD). Materials and methods. One hundred and sixty patients with NASH with comorbid type 2 DM of moderate severity and DКD stages I–IV were examined. A prospective study was conducted, which involved 160 patients and 30 practically healthy individuals. In particular, 25 patients with NASH and type 2 diabetes (group 1), 20 people with NASH and class I obesity (group 2), 70 patients with NASH stage I–IV (group 3), of whom 31 patients (44.3%) had DКD stage I–II (group 3a), 20 (28.6%) stage III (group 3b), 19 (27.1%) had DKD stage IV (group 3c). Results. In patients with NASH, type 2 DM, and DKD stage I–IV, hypoalbuminemia was found to be probably higher compared to that of patients with type 2 DM, DКD stage I–IV and without NASH that indicates the influence of NASH on the level of albuminemia; higher blood level of creatinine and urea; lower glomerular filtration rate, which confirms the negative effect of NASH on the course of type 2 DM with DКD. In the presence of NASH, patients with DКD had a higher level of albuminuria, urinary creatinine, albumin-creatinine ratio than if it’s absent. Conclusions. Indicators of the renal functional state in patients with NASH and type 2 DM varied depending on the presence of DКD and its stage. As the stage of DКD increased, the content of albumin in the blood decreased, the levels of creatinine and urea increased. The result of the detected changes was an increase in glomerular filtration rate, which indicates the phenomenon of hyperfiltration, which is specific for the initial stages of DКD.

The options of an individual approach to the modification of sinustrabeculectomy for hypotensive effect prolongation

BACKGROUND: Reducing scarring in the postoperative period is one of the main tasks of glaucoma surgery.&#x0D; AIM: To develop new modifications of sinustrabeculectomy in the surgical treatment of primary open-angle glaucoma normalizing and prolonging the outflow of aqueous humor along newly formed pathways.&#x0D; MATERIALS AND METHODS: Surgical procedures were performed in 106 patients (109 eyes) with primary open-angle glaucoma of moderate and advanced stages, without any history of previous surgeries. Patients were divided into groups: 1a 25 patients (25 eyes) who underwent sinustrabeculectomy with the formation of grooves for the intramuscular fluid outflow, 1b 26 patients (28 eyes) who underwent of sinustrabeculectomy with scleral flap twisting, 1c 28 patients(29 eyes) who underwent sinustrabeculectomy with scleral flap stitching, and the control group 27 patients (27 eyes) who underwent routine sinustrabeculectomy. The follow-up duration was up to 24 months.&#x0D; RESULTS: In 1 month after surgery, the average level of intramuscular pressure was comparable and remained low in all groups. Complete compensation of intramuscular pressure in groups 1a, 1b and 1c was observed in 80%, 75% and 76% of cases; partial in 16%, 18% and 21% of cases; failure in 4%, 7% and 3% of cases, respectively. In the control group (2), complete hypotensive success was noted in 55% of cases; partial in 30% of cases; failure in 15% of cases.&#x0D; CONCLUSIONS: Developed new methods of sinustrabeculectomy allow to obtain a prolonged hypotensive effect.

The state of the cellular link of innate immunity in men depending on type and amount of alcohol consumed

The aim. Study of the state of the cellular link of nonspecific immunity depending on the type and amount of alcohol consumed.&#x0D; Materials and methods. 110 men between the ages of 20 and 55 were examined, who were divided into 3 groups. The first (control) group consisted of 17 fertile men who do not drink alcoholic beverages. The second group (comparison) consisted of 27 patients who use, but do not abuse, all types of alcoholic beverages (1-2 doses of alcohol approximately once every 1-3 months). The third group consisted of 66 patients who abuse alcoholic beverages (6 or more units of alcohol at a time or 22 or more doses per week). Depending on the type of alcohol, this group was divided into 3 subgroups: 3a subgroup – 13 patients who abuse strong alcoholic beverages; 3b - 27 patients who abuse beer and 3c group - 26 patients who abuse beer and strong alcoholic beverages. All men underwent a survey to assess alcohol consumption during the past year, as well as an assessment of the phagocytic activity of the neutrophilic and monocyte units of the immune system with the calculation of the degree of immune system disorders.&#x0D; The results of the conducted studies showed that incomplete phagocytosis of neutrophilic and monocyte links was observed in all studied groups with preservation of the functional-metabolic reserve in groups 2 and 3a and its depletion in groups 3b and 3c. The most immunologically compromised were groups 3b and 3c, in which 1-2 degree deficiency was observed, which perhaps reflects the negative effect of beer itself on the cellular factors of innate immunity.&#x0D; Conclusion. Consumption of both strong alcoholic beverages and beer causes suppression of the phagocytic activity of neutrophils and stimulation of the absorption capacity of monocytes, which is manifested by ineffective phagocytosis. With the consumption of strong alcoholic beverages, preservation of the functional and metabolic reserve of neutrophils is observed, and with the consumption of beer and mixed alcoholic beverages, its deficiency is observed.

Antibody Response (IgM and IgG) After Two Doses of Immunization Against SARS-CoV-2 and Comparison of Two Different Third Dose Administrations

Türkiye's first SARS-CoV-2 vaccination campaign started with an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) mid-January 2021 for healthcare workers. The second dose was administered at an interval of 21 days-one month. As of July 2021 (4-4.5 months after the second dose), the Republic of Türkiye Ministry of Health suggested the third vaccination dose for healthcare workers and people over 50. The individuals could select between the choice of CoronaVac or an mRNA vaccine BNT162b2 (Pfizer‐BioNTech, Inc) for the third dose vaccination. Thus, a heterogeneous immunization emerged in society. This study is aimed to investigate the humoral response (IgG and IgM) after two doses of the SARS-CoV-2 vaccine and the possible effects of factors for this response, as well as to compare the third dose of homogeneous and heterogeneous vaccine administration. The study included 512 volunteers who are 21-65 years old that have been immunized against SARS-CoV-2 in at least two doses, working at Bursa Uludag University Faculty of Medicine Health Application and Research Center. The demographic characteristics of the participants (such as age, gender, and place of duty), background (presence of chronic disease, risky contact for SARS-CoV-2 transmission, and history of COVID-19 infection), and immunization characteristics were obtained with a questionnaire. Participants were divided into five main groups regarding the time elapsed months after the second dose and the type of vaccine administered (CoronaVac or BNT162b2). Group 1b (n=11); (blood samples were taken) one month after the second dose of BNT162b2 vaccine, group1c (n=12); one month after the second dose of CoronaVac, group 2 (n=9); two months after the second dose of CoronaVac vaccine, group 3 (n=27); three months after of CoronaVac vaccine, group 4 (n=418); four months after the second dose of CoronaVac vaccine and group 5 (n=35); five months after the second dose of CoronaVac vaccine. One month later, blood samples were taken from 52 participants in group 4 who received the third dose of the vaccine. In these participants, IgG levels were compared after two different third-dose vaccines [BNT162b2; group 4b (n=30) and CoronaVac; group 4c (n=22)]. SARS-CoV-2 IgM and IgG responses were evaluated by SARS-CoV-2 IgM (Abbott, USA) and IgG Quant II (Abbott, USA) kits on Architect i2000SR (Abbott, USA) autoanalyzer with a chemiluminescent based method at Bursa Uludag University Faculty of Medicine Medical Microbiology Laboratory. In this study, a high rate (&gt;80%) of anti-S IgG seroconversion was observed in all groups given two doses of the SARS-CoV-2 vaccine. The median IgG levels in groups 1b, 1c, 2, 3, 4, and 5 were 4315.3 AU/mL (24-10337), 721.5 AU/mL (154-1430), 842.5 AU/mL (365-4447), 183.0 AU/mL (14-1635), 165.0 AU/mL (4-31796) and 110.0 AU/mL (28-8757), respectively. After CoronaVac vaccination with two doses, groups 3, 4, and 5 had low levels of anti-SARS-CoV-2 IgG compared to group 1c (p values: 0.034, 0.006, and 0.001, respectively). IgM positivity was between 12.5-33.5% in the participants whose blood samples were obtained at one, two, and three months after the vaccination and 3.2-4.3% in the participants after four and five months (p=0.001). The heterogeneous immunization [two doses of CoronaVac and one dose of BNT162b2: median 11084.5 AU/mL (2948-40000)] has provided higher SARS-CoV-2 IgG levels compared to homogeneous immunization [three doses of CoronaVac: median 1707.0 AU/mL (304-8322)] (p&lt;0.001). When the factors that affect the vaccine response were examined four months after two doses of the CoronaVac vaccine, IgM and IgG responses were higher in participants who also had past COVID-19 infection history (p=0.001). Advanced age (&gt;60) was the most critical negative factor in IgG levels (p=0.001). Unlike previous research, it was found that the presence of comorbidity and gender did not affect the vaccine response after four months. Having a high-risk contact history and working in high-risk areas (pandemic ward) did not affect the antibody response. Among the factors evaluated, the only factor affecting IgM positivity was the combination of vaccine and natural immunity. Decreased levels of anti-S IgG antibody three months after the CoronaVac vaccine may affect the protection, especially in advanced age groups. Although this situation creates a guide for the planning of booster doses, the neutralizing antibody and T-cell response are important for protection.

Associations of Smoking, Cytomegalovirus Serostatus, and Natural Killer Cell Phenotypes in Smokers With and At Risk for COPD.

Chronic obstructive disease (COPD) risk factors, smoking and chronic infection (Cytomegalovirus (CMV)) may mold NK cell populations. What is not known is the magnitude of effect of CMV seropositivity imparts on populations in smokers with and at-risk for COPD. We investigate the independent influence of CMV seropositivity on NK cell populations and differential effects when stratifying by COPD and degree of smoking history. Descriptive statistics determine relationship between cytotoxic NK cell populations and demographic and clinical variables. Multivariable linear regression and predictive modeling was performed to determine associations between positive CMV serology and proportions of CD57+ and NKG2C+ NK cells. We dichotomized our analysis by those with a heavy smoking history, COPD, and describing the effect size of CMV seropositivity on NK cell populations. When controlled for age, race, sex, pack-years smoked, body-mass index, and lung function, CMV+ serostatus was independently associated with a higher proportion of CD57+, NKG2C+, and NKG2C+CD57+ NK cells. CMV+ serostatus was the sole predictor of larger NKG2C+ and CD57+NKG2C+ populations. Associations are more pronounced in those with COPD and heavy smokers. Among Veterans who are current and former smokers, CMV+ serostatus was independently associated with larger CD57+ and NKG2C+ populations, with a larger effect in heavy smokers and those with COPD, and was the sole predictor for increased expression of NKG2C+ and CD57+NKG2C+ populations. These findings may be broadened to include the assessment of longitudinal NK cell population change, accrued inflammatory potential, and further identification of pro-inflammatory NK cell population clusters.

Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.