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Negative-sense, single-stranded RNA (-ssRNA) viruses comprise some of the deadliest human pathogens (Ebola, rabies, influenza A viruses etc.). Developing therapeutic tools relies on a better understanding of their multiplication cycle. For these viruses, the genome replication and transcription activities most-often segregate in membrane-less environments called inclusion bodies (IBs) or viral factories. These "organelles" usually locate far from the cell surface from where new virions are released, and -ssRNA viruses do not encode for transport factors. The efficient trafficking of the genome progeny toward the cell surface is most often ensured by mechanisms co-opting the cellular machineries. In this review, for each -ssRNA viral family, we cover the methods employed to characterize these host-virus interactions, the strategies used by the viruses to promote the virus genome transport, and the current gaps in the literature. Finally, we highlight how Rab11 has emerged as a target of choice for the intracellular transport of -ssRNA virus genomes.

International audience; No abstract available

We compared PCR results from SARS-CoV-2-positive patients tested in the community in France from 14 June to 30 July 2021. In asymptomatic individuals, Cq values were significantly higher in fully vaccinated than non-fully vaccinated individuals (effect size: 1.7; 95% CI: 1–2.3; p −6). In symptomatic individuals and controlling for time since symptoms, the difference vanished (p = 0.26). Infections with the Delta variant had lower Cq values at symptom onset than with Alpha (effect size: −3.32; 95% CI: −4.38 to −2.25; p −6).

To discuss selected endocrine causes of hypertension and to provide practical clinical recommendations regarding the evaluation and treatment of these disorders. More than 15 endocrine disorders with varying rates of prevalence can cause hypertension. For example, primary aldosteronism may exist in up to 20% of patients with resistant hypertension. Recognition of these important secondary causes of hypertension is essential to provide contemporary targeted therapies in order to improve long-term disease outcomes. Clinicians must have a broad understanding of the prevalence, clinical presentation, and current diagnostic modalities for endocrine causes of hypertension to facilitate prompt referral, identification, and optimal management of these disorders. Endocrine causes of hypertension are multifactorial and, in some cases, widely prevalent. It is important for clinicians considering secondary causes of hypertension to be knowledgeable about the underlying pathophysiology of these disorders and to understand when additional evaluation and treatment may be needed.

BACKGROUND: PCOS is the most common cause of hirsutism in women of reproductive age. The presence of virilization in addition to hirsutism should alert to the possibility of less common causes of hyper-androgenization (HA) in this population including otherwise uncommon functional ovarian neoplasms (FON). We present 3 cases of women initially thought to have PCOS in whom virilization was the prime clue to the correct diagnosis of FON. Clinical Case series: Case 1 is a 40yr old woman with obesity and dysmetabolic syndrome referred for hirsutism presumed due to PCOS. She had noted symptoms over 2–3 yrs with amenorrhea and associated infertility. Examination revealed marked hirsutism and virilization with Ferriman-Galleway score (FGS) of 20. Lab tests confirmed marked male range HA. Multiple imaging tests revealed no adrenal or ovarian mass lesions. FDG-PET scan finally revealed a left ovarian focus for which she has left oophorectomy that revealed a 1cm Leydig cell tumor, Her HA resolved post-op and spontaneous periods resumed. Case 2 is a 45yr old woman referred with possible PCOS who had 5 mth history of progressive hirsutism and generalized hypertrichosis, dull lower abdominal pain and amenorrhea. Examination revealed marked hirsutism with generalized hypertrichosis and virilization. FGS was 25 and clitoral index was 935mm2. Lab tests confirmed marked male range HA and abdominopelvic imaging show no adrenal lesions but a 5.2cm left ovarian mass. Left salpingo-oophorectomy revealed a steroid cell tumor and postoperatively her androgen levels normalized. Case 3 is 37 yr old woman with SLE and obesity with prior gastric bypass referred with presumed PCOS but presenting with 1 yr history of progressive hirsutism. She was initially thought to have non classical CAH and treated with oral glucocorticoids with no symptom improvement. Examination revealed marked hirsutism, virilization with elevated FGS and clitoromegaly. Lab tests showed marked male range HA but multiple imaging studies revealed no apparent adrenal or ovarian lesions. Patient had no fertility interests and so had elective total hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed a 2.5cm left ovarian Leydig cell tumor not apparent at surgery and post op her androgen levels normalized. Conclusion: The distinction between PCOS which is ubiquitous and FON which is rare hinges on careful history and examination. Rapid onset hirsutism with virilization should prompt suspicion of FON. Marked male range HA (total serum testosterone >250ng/dl) is another “red flag” finding. Persistent radiologic search for such lesions should continue as they may not be immediately apparent on routine abdominopelvic imaging.

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon form of thyroid cancer, accounting for less than 5 % of all cases. It tends to be more clinically aggressive than differentiated thyroid cancers. While thyroidectomy is the mainstay of treatment, radioactive iodine plays an adjunctive role as well as TSH suppression with thyroid hormone. Some patients with advanced disease, may benefit from external beam radiation and/or systemic therapy. Case Description: A 94-year-old man presents with a left neck mass. His past medical history is significant for controlled hypertension. He notices a slowly growing mass while shaving over few months. He has no dysphagia, hoarseness, or shortness of breath. He has no history of radiation exposure and no family history of thyroid disease. A CT of the neck with contrast shows multiple pathologic appearing lymph nodes on the left side of the neck. The largest measures 5.4 x 4 x 3.9 cm, displacing the carotid space, and indenting the left internal jugular vein. The left lobe of the thyroid is heterogeneously enlarged compared to the right lobe with multiple irregular hypo-enhancing nodules. A fine-needle aspiration of the left cervical lymph node is positive for malignant large cells in sheets and clusters. Some clusters have a vague papillary/trabecular type arrangement. A total thyroidectomy and left level II-IV neck dissection is performed. Pathology shows multifocal poorly differentiated papillary thyroid carcinoma measuring 2.2 cm in greatest dimension with extensive necrosis. There is a background of lymphocytic thyroiditis. There is extensive vascular invasion (>4 foci) and extra-thyroidal extension invading only the strap muscles. There is metastasis to 7 of 12 examined lymph nodes. The largest metastatic deposit at level III measures 2.8 cm with extra-nodal extension. Tumor is negative for BRAF-V600, NRAS and TERT. His postoperative labs are as follows: TSH 346 (post-rhTSH) uiu/ml (0.5-5.0), free T4 0.87 ng/dl (0.6-1.15),Tg 1.0 ng/ml and anti-Tg

Bariatric surgery is effective in reducing body weight and obesity-related comorbidities. This study examined differences in the short-term effect of Roux en Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on the hedonic rating of food. Predominantly black women with complicated obesity and a BMI>50 g/m(2) completed a validated food preference questionnaire before and 1-3 months following surgery. Analysis of preference scores indicated that the preference for fat decreased with both surgeries. VSG also decreased the preference for sugar. Further studies are needed to evaluate long term effects of surgery on food preferences and to elucidate physiological mechanisms.

We present the case of a 43-year-old gentleman who presented to the emergency room with acute abdominal distension, confusion and vascular collapse. The emergent radiologic imaging obtained showed massive bilateral adrenal enlargement, but despite the initial clinical suspicion of possible overwhelming sepsis and/or massive abdominal/intralesional hemorrhage, lab tests based obtained rapidly confirmed the diagnosis of acute Addisonian crisis which responded dramatically to adrenocorticoid hormone replacement therapy and aggressive fluid resuscitation. The patient's established history of metastatic lung cancer confirmed this as a case of metastatic massive bilateral adrenal metastases with an initial presentation of acute adrenal insufficiency which is uncommon in the setting of metastatic carcinomatosis but more typically associated with lymphomas. Recognition of this clinical possibility is vital to enable rapid diagnosis and consequent life saving therapy.

Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.