Enhanced NO2 Sensitivity of Vertically Stacked van der Waals Heterostructure Gas Sensor and Its Remarkable Electric and Mechanical Tunability.

Nanodevices based on van der Waals heterostructures have been predicted, and shown, to have unprecedented operational principles and functionalities that hold promise for highly sensitive and selective gas sensors with rapid response times and minimal power consumption. In this study, we fabricated gas sensors based on vertical MoS2/WS2 van der Waals heterostructures and investigated their gas sensing capabilities. Compared with individual MoS2 or WS2 gas sensors, the MoS2/WS2 van der Waals heterostructure gas sensors are shown to have enhanced sensitivity, faster response times, rapid recovery, and a notable selectivity, especially toward NO2. In combination with a theoretical model, we show that it is important to take into account created trapped states (flat bands) induced by the adsorption of gas molecules, which capture charges and alter the inherent built-in potential of van der Waals heterostructure gas sensors. Additionally, we note that the performance of these MoS2/WS2 heterostructure gas sensors could be further enhanced using electrical gating and mechanical strain. Our findings highlight the importance of understanding the effects of altered built-in potentials arising from gas molecule adsorption induced flat bands, thus offering a way to enhance the gas sensing performance of van der Waals heterostructure gas sensors.

Metabolic Disorders During Prolactinomas.

The metabolic profile during prolactinoma may be subject to significant changes. We aimed to describe the different metabolic aspects in patients monitored for prolactinoma and to study the correlations between the size of the prolactinoma and the metabolic parameters. We conducted a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker Hospital in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. The mean age of our patients was 38.3 ± 14.2 years. They were divided into 51 women (66.2%) and 26 men (33.7%). Pituitary tumor syndrome was the most common circumstance of discovery in our population (62.3%). The clinical examination revealed an average waist circumference of 95.71 cm. Android fat distribution was observed in 25 women (49%) and 12 men (46.1%). A statistically significant positive correlation was objectified between waist circumference and tumor size (r = 0.29 and P = 0.019). The average body mass index was 28.08 kg/m2. Obesity was noted in 56 cases (72.7%). Glucose tolerance disorders and hypertriglyceridemia were also more evident each time prolactinoma size increased in contrast to the level of high-density lipoprotein cholesterol which decreased with adenoma size. Our study highlighted the metabolic and hormonal repercussions of prolactinomas. Metabolic syndrome was more common in patients with larger prolactinoma. These results should guide the initial assessment and therapeutic management of prolactin adenomas.

The anti-Müllerian hormone: A useful tool for diagnosis of Polycystic Ovary Syndrome.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disorder that affects reproductive-age women with important long-term health implications. As such, the anti-Müllerian hormone (AMH) was proposed as a helpful test to identify women with PCOS. The aim of this study was to determine an AMH cut-off value for the diagnosis of PCOS. METHODS: This was a two-year cross-sectional study including women of reproductive age, diagnosed with PCOS according to Rotterdam criteria (2003). The control group of healthy women was age-matched. AMH was performed using an electrochemiluminescence immunoassay. AMH levels were compared and evaluated with the receiver operating characteristic curve analysis. RESULTS: A total of 130 women were enrolled in this study. Of these, 65 were diagnosed with PCOS, and 65 were healthy. No significant difference was detected in body mass index between the two groups. AMH levels were significantly higher in women with PCOS (p = < 0.001). No significant difference in AMH levels was detected between PCOS phenotypes. A cut-off of 25.1 pmol/L (3.5 ng/mL) could discriminate women with PCOS from controls with a sensitivity of 74% and specificity of 72.3%. The area under the curve was 0.811 (95% CI: 0.73-0.88). CONCLUSIONS: Our study suggests that AMH had good diagnostic potential as a complement to Rotterdam criteria for PCOS diagnosis in reproductive-age women of Tunisian origin.

Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature.

Background: Papillary Thyroid Carcinoma (PTC) is the most frequent endocrine malignancy with a variety of histological presentations. Warthin-like Papillary Thyroid Carcinoma (WLPTC) is an uncommon neoplasm that is recognized as a distinct subtype of PTC in the WHO classification of thyroid tumors. In this report, we present a novel case of WLPTC in a female patient and provide an in-depth review of the available literature on its clinical, pathological, and therapeutic characteristics. Case presentation: A 27-year-old female patient was referred for neck swelling. Ultrasound showed two suspicious thyroid nodules leading to a thyroidectomy. She was diagnosed with intermediate-risk bifocal foci of classic PTC and WLPTC, arising from a background of chronic lymphocytic thyroiditis (CLT). This pT1b(m) N1b M0 malignancy was treated with adjuvant isotopic ablation and suppressive thyroxine therapy. The 1-year outcomes were favorable. Literature review: It covered articles published from 1995 to 2022, by searching PubMed and Google Scholar using specific terms. Out of 148 articles reviewed by two authors, 25 relevant articles were selected, including 13 case reports and 12 case series. The study included 150 cases of WLPTC. Data related to clinical presentation, imaging, histological features, management, and outcomes, were extracted. The mean age of diagnosis was 39 years, with a female predominance. The most common clinical presentation was neck swelling. Thyroid autoimmunity was positive in 71.6% of patients. Lymph node metastases were present in 28% of cases, with no reported distant metastases. Overall, the outcomes were favorable. Conclusion: WLPTC shares similar clinical and radiological presentations as classic PTC. The hallmark histological features of WLPTC are papillae lined with oncocytic tumor cells with papillary nuclear changes and lymphoid stroma. WLPTC is almost constantly associated with CLT. The management of WLPTC aligns with that of classic PTC with comparable stage and risk category, often resulting in favorable outcomes.

Insulinoma with equivocal imaging.

Summary: A 55-year-old patient was admitted to our department for the management of a repetitive alteration of consciousness. Biological investigation results were consistent with endogenous hyperinsulinemic hypoglycemia. Insulinoma was therefore suspected. Abdominal computed tomography and endoscopic ultrasound showed no obvious pancreatic mass.Somatostatin receptor scintigraphy showed abnormal radioactive uptake in both the pancreatic tail and the uncinate process. Contrariwise, abdominal magnetic resonance imaging showed a unique lesion in the pancreas tail. The patient was then proposed for pancreatic surgery. Both intraoperative manual palpation and intraoperative ultrasonography of the pancreas showed a single corporal lesion of 1.5 cm. No lesion was found in the uncinate process. After a left pancreatectomy, the lesion was histopathologically confirmed to be a well-differentiated neuroendocrine tumor. The symptoms of the patient resolved almost immediately following the surgery. The follow-up is one and a half years to date. Learning points: The exact preoperative localization of the pancreatic mass remains the most challenging part of insulinoma diagnostic workup. The radiologist's experience is the best warrantor to a precise localization of the tumor. 111In-DTPA-octreotide uptake in the pancreatic uncinate process may be physiological and its interpretation must, therefore, be vigilant. Manual palpation along with intraoperative ultrasonography is considered as the most effective method for the localization of insulinomas during open surgery.

Health-related quality of life in long-term differentiated thyroid cancer survivors: A cross-sectional Tunisian-based study.

Background and Aim: The incidence of differentiated thyroid cancer (DTC) has risen dramatically worldwide. Despite an excellent prognosis, the growing DTC survivors' community often features poor health-related quality of life (HRQoL), which challenges long-term DTC care, particularly in developing Southern Mediterranean and African countries. We aimed to assess the HRQoL and to investigate its determinants in disease-free Tunisian DTC survivors. Methods: We conducted a three-month cross-sectional study that included 266 patients diagnosed with DTC. We assessed the HRQoL in eligible participants using the short form-36 health survey, in comparison with 76 healthy controls. Results: The 86 eligible DTC survivors were predominantly female (89.5%) with an average age of 44.3 ± 12.5 years. Physical-functioning (PF), role-physical (RP), and pain domains were substantially altered compared to the reference population. Age was negatively associated with PF, RP, role-emotional (RE), and social functioning (SF). Tumor size and lymph node metastases affected general health and PF, respectively. The cancer-free survival duration was positively correlated with mental health (MH). Poor neck scar healing and persistent post-operative hypoparathyroidism significantly deteriorate MH. Pain perception was positively correlated with the radioactive iodine cumulative dose. Subclinical hyperthyroidism significantly reduced PF and RP scores. TSH suppression was negatively and strongly correlated with MH and SF scores. Conclusion: HRQoL is substantially reduced in DTC survivors compared to the normative Tunisian population. These results could be extrapolated to similar individuals in other South Mediterranean and African countries. The development of coordinated multidisciplinary aftercare interventions in this region is warranted to preserve HRQoL in DTC survivors.

Pheochromocytoma of the prostate: An unusual location.

Ectopic pheochromocytomas, also called paragangliomas, are defined as catecholamine -secreting tumors, which develop outside the adrenal medulla. Pheochromocytomas of the urinary tract represent less than 1% of all paragangliomas and are most commonly located in the bladder. Nevertheless, prostatic pheochromocytoma is an extremely rare clinical entity and only a few cases have been reported in the medical literature. Herein, we report a case of ectopic pheochromocytoma arising from the prostate, revealing with hypertensive crisis occurring immediately after ejaculation.

Pituitary MRI Features in Acromegaly Resulting From Ectopic GHRH Secretion From a Neuroendocrine Tumor: Analysis of 30 Cases.

CONTEXT: Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series. OBJECTIVE: Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly. DESIGN: Multicenter, international, retrospective. SETTING: Tertiary referral pituitary centers. PATIENTS: Thirty ectopic acromegaly patients having GHRH hypersecretion. INTERVENTION: None. MAIN OUTCOME MEASURE: MRI characteristics of pituitary gland, particularly T2-weighted signal. RESULTS: In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize. CONCLUSIONS: This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis.

Posterior short segment pedicle screw fixation for the treatment of thoracolumbar fracture.

The choice of the type of stabilization device in the osteosynthesis of dorso-lumbar spine fractures remains a subject of controversy. The present study aims to evaluate the efficiency of short segment in patients suffering post-traumatic thoracolumbar fractures. This study was conducted in the Department of Orthopedic Surgery and Traumatology of the Habib Bourguiba University Hospital, Sfax, Tunisia. All our patients had a spinal osteosynthesis via the posterior approach with a short segment pedicle screw fixation. We established a record of the pre and post-operative data, the functional results in the post-operative stage during the follow-up period and in retrospect according to the Denis Pain Scale, as well as the Oswestry score. The correction was evaluated by determining the relative gain and loss at the last period of retrospect: vertebral kyphosis, regional kyphosis, Gardner Segment Kyphotic Deformity (GSKD), and computed tomography (CT) scan in retrospect to check the quality of the arthrodesis. The average Oswestry score was 14%. Twenty-nine patients had an Oswestry score ≤40%. The relative gain obtained postoperatively was 57.3% for vertebral kyphosis, 67.2% for regional kyphosis and 71.3% for Gardner kyphosis deformity; while the loss of correction at the last follow-up was 0.6° for vertebral kyphosis, 1.5° for regional kyphosis and 0.9° for GSKD. No cases of non-union were reported. The short segment fixation makes it possible to limit operating time, the abundance of bleeding and the aggression of the soft tissues.

A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report.

VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

Homozygous pArg610del Mutation Unusually Associated With Severe Delay of Growth in 2 Acid Sphingomyelinase Deficiency-affected Sibs.

BACKGROUND: Typically, patients with Acid Sphingomyelinase Deficiency (ASMD) because of p.Arg610del mutation, have mild phenotype with normal linear growth. OBSERVATION: We reported the case of 2 Tunisian brothers who have been referred for splenomegaly, polyadenopathies, pubertal, and growth delay. Molecular testing of SMPD1 gene revealed the presence of a homozygous p.Arg610del mutation. Lysosphingomyelin and its isoform-509 were both increased confirming ASMD for both cases. Growth hormone deficiency was highly suspected but growth hormone response after stimulating tests was acceptable for both patients. CONCLUSIONS: There is no correlation between phenotype-genotype in case of p.Arg610del mutation that could be associated to a severe delay of growth.

[Insulinoma associated with adrenocorticotropic insufficiency and hypergonadotropic hypogonadism: a case study]. / Insulinome associé à une insuffisance corticotrope et un hypogonadisme hypergondadotrope: à propos d'une observation.

Pancreatic insulinoma is a rare, often benign, neuroendocrine tumor which may give rise to life-threatening consequences due to hypoglycemia-related accidents. Adrenal deficiency can also cause hypoglycemia. We report the case of a 68-year old patient hospitalized for recurrent hypoglycaemia. Tests were performed that showed endogenous hyperinsulinism, adrenocorticotropin deficiency and hypergonadotropic hypogonadism. The patient received hydrocortisone without improvement. Five years later topography showed insulinoma. This study highlights the clinical, biological, radiological and therapeutic features of insulinoma as well as laboratory test results and shows that insulinoma can cause adrenocorticotropic deficiency and peripheral hypogonadism.

Nonstop mutation in the Kisspeptin 1 receptor (KISS1R) gene causes normosmic congenital hypogonadotropic hypogonadism.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder mostly characterized by gonadotropins release and/or action deficiencies. Both isolated (idiopathic hypogonadotropic hypogonadism) and syndromic (Kallmann) forms are identified depending on the olfactory ability. Clinical and genetic heterogeneities of CHH have been widely explored, thus improving our understanding of the disease's pathophysiology. This work aims to (1) provide a detailed clinical and hormonal description of normosmic CHH patients and (2) identify the mutation linked to the studied phenotype. PARTICIPANTS AND METHODS: We investigated three affected patients with normosmic CHH, belonging to a consanguineous Tunisian family. Patients underwent an insulin-induced hypoglycemia test. We performed whole exome sequencing to identify the causal mutation. RESULTS: At first diagnosis, a total gonadotropic deficiency was identified in all patients. The insulin-induced hypoglycemia test has also revealed a reduced cortisol secretion and complete growth hormone deficiency. At 20.8 years, one female exhibited a spontaneous recovery of the hypothalamic-pituitary-adrenal axis function, unlike her affected siblings who still depend on corticosteroid replacement therapy. Herein, we identified a novel homozygous nonstop mutation (c.1195T>C) in KISS1R gene in all affected subjects. This mutation led to the substitution of the physiologic stop codon by an arginine (p.X399R). CONCLUSIONS: Our study highlights the importance of the KISS1R signaling, in gonadotropin-releasing hormone neurons, in the control of reproductive function. Additionally, our data suggests a complex central and peripheral metabolic control of puberty, through the hypothalamic KISS1R signaling. We suggest a mutual link between the hypothalamic-pituitary-gonadal, -adrenal, and -somatotropic axes.

Fahr's syndrome in Southern Tunisia: A broad spectrum of clinical and etiological features.

AIM: We describe the clinical and etiological profile of patients with Fahr's syndrome (FS). METHODS: Charts of sixteen patients diagnosed with FS between 1999 and 2014 were retrospectively assessed. RESULTS:   The mean age at diagnosis was 44.68 years (11-67 years). The most main presenting neurological features were seizures in 6 cases, headaches in 5 cases and parkinson's syndrome in 3 cases. Psychiatric disorders were observed in 2 patients including memory loss and iritability. Hypocalcemia clinical features were observed in 7 cases. The mean value of hypocalcemia was 1.69 mmol/l. Etiologies included idiopathic hypoparathyroidism in 4 patients, pseudohypoparathyroidism in 5 cases, secondary hypoparathyroidism, isolated hypovitaminosis D and cerebral radiotherapy in one case for each and Fahr's disease in 4 patients.  Oral calcium and vitamin D substitution were started in patients with parathyroid disturbances with favorable outcome. CONCLUSION: In this report, we propose to discuss the clinical manifestations of FS, its etiologies especially parathyroid disturbances and its therapeutic modalities.

Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction (VED) is considered as a common complication among people with type 2 diabetes (T2D). We tested whether changes in fatty acid (FAs) classes measured in erythrocytes are associated with increased risk of diabetic VED along with related risk factors. METHODS: We assessed erythrocyte FAs composition, lipid peroxidation parameters and inflammatory cytokines among 72 T2D men with VED, 78 T2D men without VED and 88 healthy volunteers with similar age. Biochemical, hepatic, lipid and hormonal profiles were measured. RESULTS: T2D people with VED had significant decrease in the indexes of Δ6-desaturase and elongase activities compared to the other studied groups. The same group of participants displayed lower erythrocytes levels of dihomo-γ-linolenic acid (C20:3n-6) (P < .001), precursor of the messenger molecule PGE1 mainly involved in promoting erection. Moreover, absolute SFAs concentration and HOMA IR levels were higher in T2D people with VED when compared to controls and associated with impaired NO concentration (1.43 vs 3.30 ng/L, P < .001). Our results showed that IL-6 and TNF-α were significantly increased and positively correlated with MDA levels only in T2D people with VED (r = 0.884, P = .016 and r = 0.753, P = .035; respectively) suggesting a decrease in the relative availability of vasodilator mediators and an activation of vasoconstrictors release. CONCLUSION: Our findings show that the deranged FAs metabolism represents a potential marker of VED in progress, or at least an indicator of increased risk within men with T2D.

A comparative study of nuclear 8-hydroxyguanosine expression in Autoimmune Thyroid Diseases and Papillary Thyroid Carcinoma and its relationship with p53, Bcl-2 and Ki-67 cancer related proteins.

PURPOSE: To investigate whether the oxidative stress is involved in the evolution of Graves' disease (GD) and Hashimoto thyroiditis (HT) into Papillary Thyroid Carcinoma (PTC), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cancer related proteins (Bcl-2, p53 and Ki-67) expressions were evaluated in these pathologies. PATIENTS AND METHODS: Immunohistochemical method was applied on 25 thyroid tissues. Allred score (AS) serving to evaluate the immunostaining is based on a scale from 0 to 8. "Negligible expression" was assigned to a score of 0 to 2, "expression" and "overexpression" were attributed to a score of 3-5 and ≥6 respectively. RESULTS: PTC cancer cells exhibited 100% 8-OHdG "overexpression" compared to 87.5% in PTC non-malignant epithelial (NME) ones (p<0.05). Higher 8-OHdG AS was found in PTC NME cells compared to GD and HT (p<0.001, p<0.05 respectively). "Overexpression" of Bcl-2 was noted in all PTC cell types. Remarkably, just like the PTC cancer and NME cells 33.3% of HT and 50% of GD patients' revealed simultaneous "overexpression" of Bcl-2 and 8-OHdG in epithelial cells. No staining was detected for p53 in all pathologies. PTC lymphoid cells exhibited 100% "overexpression" for 8-OHdG and Bcl-2 with concomitant "negligible expression" for Ki-67 in 87.5% of patients. In contrast, HT lymphoid cells showed 22.2% "expression" and GD 62.5% "expression" and 12.5% "overexpression" of Ki-67. CONCLUSIONS: Simultaneous "overexpression" of 8-OHdG and Bcl-2 in GD and HT could be considered as prognostic markers while "negligible expression" of Ki-67 in PTC lymphoid cells suggests an anergic state favoring the tumor escapes from the immune system.

Clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 expression in Tunisian gastric adenocarcinomas.

Gastric carcinoma (GC) is a highly aggressive malignancy with poor prognosis. It is widely accepted that malignancy results from abnormal cell growth due to dysregulation of the balance between cell proliferation and apoptosis. Our study aimed to investigate the clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 in Tunisian GC patients by immunohistochemistry. It was observed that the older patients showed p53 overexpression compared with the younger patients (p<0.05). There was higher p53 expression in the intestinal-type compared with the diffuse-type (p<0.05), and in well/moderate differentiated than in poor differentiated tumors. The expression of Ki-67 was positively associated with tumor size and venous invasion (p<0.05). Bcl2 expression occurred in male patients and correlated with depth of invasion (p=0.02). A Kaplan-Meier analysis indicated an inverse correlation between p53 and Ki-67 expression and the overall survival. Multivariate analysis revealed that the tumor site, Ki-67 and p53 expression were independent prognostic factors for gastric carcinomas (p<0.05). Finally, combined expression of p53, Ki-67 and Bcl-2 showed that the group of patients with tumors p53+/Ki-67+/Bcl2- had aggressive behavior and poor prognosis (p log rank=0.000). In summary, our data indicated that the expression of p53, Ki-67, and Bcl-2 may provide useful information for identifying patients with aggressive behavior and poor prognosis of GC.

Adrenal diseases during pregnancy: pathophysiology, diagnosis and management strategies.

: Adrenal diseases--including disorders such as Cushing's syndrome, Addison's disease, pheochromocytoma, primary hyperaldosteronism and congenital adrenal hyperplasia--are relatively rare in pregnancy, but a timely diagnosis and proper treatment are critical because these disorders can cause maternal and fetal morbidity and mortality. Making the diagnosis of adrenal disorders in pregnancy is challenging as symptoms associated with pregnancy are also seen in adrenal diseases. In addition, pregnancy is marked by several endocrine changes, including activation of the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis. The aim of this article was to review the pathophysiology, clinical manifestation, diagnosis and management of various adrenal disorders during pregnancy.

Reproductive outcomes of female patients with congenital adrenal hyperplasia due to 21-hydroxylase defi ciency.

Fertility in women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) appears to be reduced, especially in women with the classic salt-wasting type. Several factors have been suggested to contribute to this subfertility such as androgen excess, adrenal progesterone hypersecretion, consequences of genital reconstructive surgery, secondary polycystic ovaries syndrome, and psychosexual factors. In contrast to this subfertility, pregnancies are commonly normal and uneventful. Adequate glucocorticoid therapy and improvement of surgical and psychological management could contribute to optimize fertility in CAH female patients, even among women with the classic variant. This review provides current information regarding the reproductive outcomes of women with CAH due to 21-OHD and the fertility and pregnancy issues in this population.