Self-stigma, religiosity, and perceived social support in people with recent-onset psychosis in the Islamic Republic of Iran: Associations with symptom severity and psychosocial functioning.

AIMS: Most evidence on psychosocial factors in recent-onset psychosis comes from high-income countries in Europe, Australia, Canada and the USA, while these factors are likely to differ under varying sociocultural and economic circumstances. In this study, we aimed to investigate associations of self-stigma, religiosity and perceived social support with symptom severity and psychosocial functioning in an Iranian cohort of people with recent-onset psychosis (i.e. illness duration of <2 years). METHODS: We used baseline data of 361 participants (N = 286 [74%] male, mean age = 34 years [Standard Deviation = 10.0]) from the Iranian Azeri Recent-onset Acute Phase Psychosis Survey (ARAS). We included assessments of self-stigma (Internalized Stigma of Mental Illness, ISMI), religiosity (based on Stark & Glock), perceived social support (Multidimensional Scale of Perceived Social Support, MSPSS), symptom severity (Positive And Negative Syndrome Scale, PANSS) and psychosocial functioning (clinician-rated Global Assessment of Functioning Scale, GAF, and self-reported World Health Organization Disability Assessment Schedule 2.0, WHODAS 2.0). Descriptive analyses were employed to characterize the study sample. Covariate-adjusted ordinal and multivariable linear regression analyses were performed to investigate cross-sectional associations of baseline ISMI, religiosity and MSPSS with concurrent PANSS, GAF and WHODAS 2.0. RESULTS: Higher self-stigma was associated with poorer self-reported functioning (B = 0.375 [95% Confidence Interval (CI): 0.186, 0.564]) and more severe concurrent symptoms (B = 0.436 [95% CI: 0.275, 0.597]). Being more religious was associated with poorer clinician-rated functioning (OR = 0.967 [95% CI: 0.944, 0.991]), but with less severe symptoms (B = -0.258 [95% CI: -0.427, -0.088]). Stronger social support was associated with poorer clinician-rated (OR = 0.956 [95% CI: 0.935, 0.978]) and self-reported functioning (B = 0.337 [95% CI: 0.168, 0.507]). CONCLUSION: This study shows that self-stigma, religiosity and perceived social support were associated with symptom severity and clinician-rated as well as self-reported psychosocial functioning in an Iranian cohort of people with recent-onset psychosis. The findings extend previous evidence on these psychosocial factors to one of the largest countries in the Middle East, and suggest that it may be worthwhile to develop strategies aimed at tackling stigma around psychosis and integrate the role of religiosity and social support in mental ill-health prevention and therapy.

Treatment of Urethral Intercourse and Impact on Female Sexual Function.

BACKGROUND: Urethral intercourse is a very rare entity which usually presents as urinary incontinence during and after intercourse and is most commonly seen in patients with vaginal agenesis (Mayer-Rokitansky-Hauser Syndrome) or hypoplasia, or other rear vaginal anomalies. AIM: To evaluate management and outcomes for vaginal and urethral consequences of urethral intercourse, including urinary incontinence. METHODS: Between February 2006 and March 2021, 8 women aged from 17 to 22 years underwent genital and urethral reconstruction due to consequences of urethral sexual intercourse. Vaginal reconstruction included sigmoid vaginoplasty and introitoplasty with division of the vaginal septum in cases of vaginal agenesis (5 cases) and vaginal duplication (3 cases), respectively. Incontinence was treated by sling procedures in 5 women with longer history of urethral coitus and evident bladder neck prolapse. OUTCOMES: Sexual and psychosexual outcomes assessment was based on the Female Sexual Function Index and standardized questionnaires. RESULTS: Follow-up ranged from 9 to 188 months (mean 78 months). Good esthetical and functional results were achieved in all 8 women. All patients reported satisfactory sexual intercourse. All 5 incontinent women who had underwent sling procedure were continent. In one of 3 nontreated cases, additional sling treatment was indicated 6 months after vaginal reconstruction with satisfactory outcome. One patient with vaginal duplication reported a successful pregnancy with a Caesarean section delivery. CLINICAL IMPLICATIONS: Urinary incontinence with megalourethra in young women, along with the presence of Mullerian anomalies should raise suspicion of urethral coitus. Surgical treatment includes correction of vaginal anomalies and management of consequences. STRENGTHS AND LIMITATIONS: This study represents one of the largest series for urethral intercourse, with assessment of psychosexual outcome. The limitation is the lack of statistical analysis due to small sample size. CONCLUSION: Urethral intercourse is very rare, but it can cause severe consequences. It is important to recognize this occurrence and treat it by well-known vaginal or urethral reconstructive procedures. Djordjevic ML, Bizic M, Stojanovic B, et al. Treatment of Urethral Intercourse and Impact on Female Sexual Function. Sex Med 2022;10:100534.

Untreated PKU patients without intellectual disability: SHANK gene family as a candidate modifier.

Phenylketonuria (PKU) is an inborn error of metabolism caused by variants in the phenylalanine hydroxylase (PAH) gene and it is characterized by excessively high levels of phenylalanine in body fluids. PKU is a paradigm for a genetic disease that can be treated and majority of developed countries have a population-based newborn screening. Thus, the combination of early diagnosis and immediate initiation of treatment has resulted in normal intelligence for treated PKU patients. Although PKU is a monogenic disease, decades of research and clinical practice have shown that the correlation between the genotype and corresponding phenotype is not simple at all. Attempts have been made to discover modifier genes for PKU cognitive phenotype but without any success so far. We conducted whole genome sequencing of 4 subjects from unrelated non-consanguineous families who presented with pathogenic mutations in the PAH gene, high blood phenylalanine concentrations and near-normal cognitive development despite no treatment. We used cross sample analysis to select genes common for more than one patient. Thus, the SHANK gene family emerged as the only relevant gene family with variants detected in 3 of 4 analyzed patients. We detected two novel variants, p.Pro1591Ala in SHANK1 and p.Asp18Asn in SHANK2, as well as SHANK2:p.Gly46Ser, SHANK2:p.Pro1388_Phe1389insLeuPro and SHANK3:p.Pro1716Thr variants that were previously described. Computational analysis indicated that the identified variants do not abolish the function of SHANK proteins. However, changes in posttranslational modifications of SHANK proteins could influence functioning of the glutamatergic synapses, cytoskeleton regulation and contribute to maintaining optimal synaptic density and number of dendritic spines. Our findings are linking SHANK gene family and brain plasticity in PKU for the first time. We hypothesize that variant SHANK proteins maintain optimal synaptic density and number of dendritic spines under high concentrations of phenylalanine and could have protective modifying effect on cognitive development of PKU patients.

Liver anatomy, intrahepatic vascular and biliary branching system of the mole rat (Spalax leucodon).

BACKGROUND: There are many studies on the morphology of the liver and its blood vessels in experimental animals, but such studies are lacking in the mole rat (Spalax leucodon). The aim of this paper was a detailed basic study on the topography, morphology, vascular and biliary branching systems of the liver in the mole rat. MATERIALS AND METHODS: Coloured gelatine and mixture of coloured lead oxide and linseed oil were injection contrast masses used to obtain vascular and biliary branching pattern in the liver. It was revealed that the liver of the mole rat had five lobes (left, quadrate, right medial, right lateral and caudate lobes). RESULTS: The left, undivided lobe was the largest lobe of the liver. The quadrate lobe was divided into two components by a deep notch. The gallbladder, of cylindrical shape, was present and attached to the quadrate lobe. The common bile duct was formed by the union of the left and right hepatic ducts. The pancreatic duct joined the common bile duct before it entered the duodenum. In the present study, only the right medial lobe and quadrate lobe always showed a single lobar artery, portal and hepatic veins. The left lobe showed four lobar arteries, portal and hepatic veins. The caudate lobe with its two processes and the right lateral and medial lobes had different arterial and portal blood supply as well as hepatic and biliary drainage of these lobes. The intrahepatic branches of the proper hepatic artery ran parallel to the branches of the common portal vein in the same lobes of the liver. CONCLUSIONS: The results of this study are significant for comparative studies among different species of rodents and other experimental animals. Morphology, vasculature and biliary tract of the liver in the mole rat were similar to that of other experimental animals and identified differences may be related to the adaptation to the mode of life and diet of this rodent.

Ambiguous Genitalia and Lissencephaly in A 46,XY Neonate with a Novel Variant of Aristaless Gene.

Introduction: Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation: A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions: The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Hysterectomy with Bilateral Salpingo-Oophorectomy in Female-to-Male Gender Affirmation Surgery: Comparison of Two Methods.

INTRODUCTION: The optimal route for hysterectomy with bilateral salpingo-oophorectomy in female-to-male gender affirmation surgery is still under debate, due to the quite limited and inconsistent published data. The aim of this study is to present and compare the results of vaginal and laparoscopic hysterectomy as part of gender affirmation surgery in female-to-male transsexuals. MATERIALS AND METHODS: Between 2012 and 2017, 124 female-to-male transsexuals, aged 18-43 years (mean age: 28.5), underwent hysterectomy with bilateral salpingo-oophorectomy, followed by colpocleisis and gender affirmation surgery. Transvaginal and laparoscopic hysterectomy were performed in 92 and 32 patients, respectively. Standard outcome measures (types and rates of complications, operative time, blood loss, and postoperative hospital stay) were used to compare the two groups of patients. RESULTS: The mean follow-up was 41 months (ranged from 6 to 65 months). The duration of transvaginal approach was significantly shorter (51 minutes compared to 76 minutes, p < 0.001). The total complication rates (less than 3%), reoperation rates (0%), blood loss, and postoperative hospital stays (4.3 days compared to 4.5 days) showed no statistical difference. CONCLUSIONS: Both approaches are safe, with minimal complications. However, we prefer transvaginal hysterectomy due to its shorter operative time, cost-effectiveness, and simpler continuation with one-stage female-to-male gender affirmation surgery.

Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants.

Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX, cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172 746 and 1:60 461 live-births, respectively. Two variants were identified in G6PC gene: c.247C>T (p.Arg83Cys) and c.518T>C (p.Leu173Pro). In SLC37A4 gene, 6 variants were detected. Three previously reported variants c.81T>A (p.Asn27Lys), c.162C>A (p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all analyzed alleles. Computational, transcription studies and/or clinical presentation in patients confirmed pathogenic effect of 3 novel variants: c.248G>A (p.Gly83Glu), c.404G>A (p.Gly135Asp) and c.785G>A (p.Ser263Glyfs*33 or p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive were the most frequent presenting signs of GSD Ia, while hepatomegaly and recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib patients developed neutropenia while 20.6% developed inflammatory bowel disease. Our study revealed the highest worldwide incidence of GSD Ib. Furthermore, description of 3 novel variants will facilitate medical genetic practice.

Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1 F) were included in the study (median age 11.0 years, range 1.2-43 years). Birth prevalence ranged from 1:69,223 (Serbia) to 1:192,626 (Czech Rep.). In the majority of patients (71%), the disease manifested in infancy. Cognitive functions were normal in 10 patients. Four, six and 24 patients had mild, moderate, and severe developmental delay, respectively, typically subsequent to developmental regression (59%). Residual enzyme activity showed no predictive value, and estimation of glycosaminoglycans (GAGs) had only limited importance for prognosis. Mutation analysis performed in 36 families led to the identification of 12 novel mutations, eight of which were small deletions/insertions. Large deletions/rearrangements and all but one small deletion/insertion led to a severe phenotype. This genotype-phenotype correlation was also identified in six cases with recurrent missense mutations. Based on patient genotype, the severity of the disease may be predicted with high probability in approximately half of MPS II patients.

Heavy-flavour and quarkonium production in the LHC era: from proton-proton to heavy-ion collisions.

This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the proton and nucleus structure at high energy to deconfinement and the properties of the Quark-Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton-proton, proton-nucleus and nucleus-nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photoproduction in nucleus-nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7[Formula: see text] Framework Programme.

Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases.

Trichinella infection in Serbia in the first decade of the twenty-first century.

In Serbia, infection with Trichinella spp. has been recognized as a human health and animal husbandry problem for almost a century. The rate of swine infection gradually decreased from 0.14% to 0.02% between 2001 and 2010. For the past 5 years, Trichinella infections among swine were detected at levels higher than 0.05% in 3 districts of Serbia while prevalence persisted at lower levels for the rest of the country. During this 10-year period, there were 2257 cases of human trichinellosis, including 3 deaths; however, a significant decrease in the number of cases was reported during the last 5 years (fewer than 200 cases per year). The fact that prevalence data presented here are similar to prevalence data from 1990 indicates that this period of 10 years was needed to overcome the re-emergence of Trichinella infection in swine and humans that occurred during the last decade of the previous century.

Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease.

INTRODUCTION: Therapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy. AIM: To benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology). METHODS: In an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9 months (60 U/kg infusion every other week [EOW]). Eleven patients completed the study and 10 enrolled in a long-term extension. After 1 year, patients who achieved ≥ 2 hematological or organ goals began step-wise dose reduction from 60 to 45 then 30 U/kg EOW. Data for anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology at baseline and 4 years are available for 8 patients (3 male, 5 female). The proportion of patients at goal for anemia, thrombocytopenia, hepatomegaly and splenomegaly at baseline was compared with the proportion achieving each goal at 4 years. The proportion achieving the skeletal pathology goal was determined on the basis of Z-score improvement from baseline to 4 years. The proportion of patients who achieved all 5 goals at 4 years was compared with the proportion at goal for all 5 parameters at baseline. RESULTS: At baseline, no patient was at goal for all clinical parameters. After 1 year of treatment, all patients maintained goals present at baseline, and all achieved ≥ 2 goals. All 8 patients began step-wise dose reduction from 60 to 30 U/kg EOW between 15 and 18 months. By year 4 of treatment, all patients met goals for all 5 clinical parameters; therefore 100% achievement was seen for each of the 5 long-term, therapeutic goals. DISCUSSION: In this velaglucerase alfa Phase I/II and extension study, clinically meaningful achievement of each long-term, therapeutic goal was observed for each patient, despite dose reduction after 1 year. This is the first report of a cohort where all patients receiving ERT for type 1 Gaucher disease achieved all 5 of these long-term, therapeutic goals within 4 years of starting treatment and after ≥ 2years dose reduction.

Subarachnoid morphine, bupivacaine and fentanyl as part of combined spinal-epidural analgesia for low anterior resection. A prospective, randomised, double-blind clinical trial.

This study was designed to compare the efficacy of subarachnoid morphine alone or in combination with bupivacaine and fentanyl for combined spinal-epidural analgesia in colorectal surgery. This is a prospective, randomised, double-blind clinical trial. Sixty patients undergoing low anterior resection were assigned to one of three groups: subarachnoid morphine, bupivacaine and fentanyl, subarachnoid morphine and bupivacaine or subarachnoid morphine only. Epidural catheter placement and subarachnoid injection were done via a combined spinal-epidural Epistar needle at L2-3. The epidural catheter was used for scheduled intraoperative bupivacaine and intermittent postoperative bupivacaine and morphine administration. Intraoperative epidural bupivacaine, intraoperative intravenous fentanyl use, time to first analgesia request, postoperative visual analogue scale pain scores, tramadol requirements and side-effects were recorded for 72 hours. Postoperative analgesia was comparable in all groups. Intraoperative fentanyl and bupivacaine consumption was lowest in the morphine, bupivacaine and fentanyl group. Time to first analgesia request was longer in the morphine, bupivacaine and fentanyl compared to the morphine group (P = 0.009). Tramadol use was lower in the morphine and bupivacaine group compared to morphine, bupivacaine and fentanyl (P = 0.017) on postoperative day two. There were no significant adverse effects. All patients ambulated the morning after surgery. The addition of bupivacaine and fentanyl to subarachnoid morphine did not confer any advantage on postoperative visual analogue scale scores and tramadol use, but lowered the need for additional intraoperative intravenous fentanyl and epidural bupivacaine and prolonged the time to first analgesia request.

Urethral Lengthening in metoidioplasty (female-to-male sex reassignment surgery) by combined buccal mucosa graft and labia minora flap.

OBJECTIVES: To develop a technique for urethral reconstruction using a combined labia minora flap and buccal mucosa graft. Urethral lengthening is the most difficult part in female transsexuals and poses many challenges. METHODS: From April 2005 to February 2008, 38 patients (aged 19-53 years) underwent single-stage metoidioplasty. The technique starts with clitoral lengthening and straightening by division of both clitoral ligaments dorsally and the short urethral plate ventrally. The buccal mucosa graft is quilted to the ventral side of the corpora cavernosa between the native orifice and the tip of the glans. The labia minora flap is dissected from its inner surface to form the ventral aspect of the neourethra. All suture lines are covered by the well-vascularized subcutaneous tissue originating from the labia minora. The labia majora are joined in the midline and 2 silicone testicular implants are inserted to create the scrotum. The neophallus is covered with the remaining clitoral and labial skin. RESULTS: The median follow-up was 22 months (range 11-42). The median neophallic length was 5.6 cm (range 4-9.2). The total length of the neourethra was 9.4-14.2 cm (median 10.8). Voiding while standing was reported by all 38 patients, and temporary dribbling and spraying were noted by 12. Two fistulas and one urethral erosion resulted from the testicular implant and required secondary revision. CONCLUSIONS: A combined buccal mucosa graft and labia minora flap present a good choice for urethral reconstruction in female-to-male transsexuals, with minimal postoperative complications.

Energy equilibration processes of electrons, magnons, and phonons at the femtosecond time scale.

We relate the energy dissipation processes at the femtosecond (electron-spin relaxation time tau el-sp) and nanosecond time scale (Gilbert relaxation taualpha) to the microscopic model proposed by Koopmans [Phys. Rev. Lett. 95, 267207 (2005)]. At both time scales, Elliot-Yafet scattering is proposed as the dominant contribution. We controllably manipulate the energy dissipation by transition metal doping (Pd) and rare earth doping (Dy) of a Permalloy film. While a change in taualpha of more than a factor of 2 is observed, tau el-sp remains constant. We explain the discrepancies as due to relaxation channels not considered in the model.

One-stage repair of severe hypospadias using combined buccal mucosa graft and longitudinal dorsal skin flap.

AIM OF THE STUDY: Urethral reconstruction in severe hypospadias presents a great challenge. We evaluated a method of combining longitudinal dorsal island skin flap and buccal mucosa graft to create a neourethra in the most severe hypospadias. Our aim was to repair the most difficult cases in a one-stage procedure. METHODS: Between January 2003 and July 2007, 23 patients (aged from 9 to 26 months) underwent repair of severe hypospadias (18 penoscrotal and 5 scrotal forms). The short urethral plate is divided in all cases and the remaining curvature was repaired by dorsal plication. The buccal mucosa graft is harvested and fixed to the ventral side of corpora cavernosa to form the first half of the neourethra. A longitudinal dorsal island skin flap is created and buttonholed ventrally. It is sutured to the buccal mucosa graft to form the neourethra. An abundant flap pedicle is fixed laterally to cover all the suture lines of the neourethra. Penile skin reconstruction is done using available penile skin. RESULTS: The mean follow-up was 27 (range 11-66) months. Satisfactory results were achieved in 20 patients. There were two urethral fistula and one temporary distal urethral stricture. CONCLUSION: A combined longitudinal island skin flap and buccal mucosa graft could be a good choice for single-stage urethral reconstruction in the repair of the most severe hypospadias.