Social responses to a hurricane drive greater epidemic risk.

The increasing frequency and intensity of extreme weather events due to climate change has the potential to alter ecosystem dynamics and wildlife health. Here we show that increasing social connections in response to a hurricane enhanced disease transmission risk for years after the event in a population of rhesus macaques. Our findings reveal that behavioural responses to natural disasters can elevate epidemic risk, thereby threatening wildlife health, population viability, and spillover to humans.

The influence of training status and parasympathetic blockade on the cardiac rate, rhythm, and functional response to autonomic stress.

Apnea (breath-holding) elicits co-activation of sympathetic and parasympathetic nervous systems, affecting cardiac control. In situations of autonomic co-activation (e.g., cold water immersion), cardiac arrhythmias are observed during apnea. Chronic endurance training reduces resting heart rate in part via elevation in parasympathetic tone, and has been identified as a risk factor for development of arrhythmias. However, few studies have investigated autonomic control of the heart in trained athletes during stress. Therefore, we determined whether heightened vagal tone resulting from endurance training promotes a higher incidence of arrhythmia during apnea. We assessed the heart rate, rhythm (ECG lead II), and cardiac inotropic (speckle-tracking echocardiography) response to apnea in 10 endurance trained and 7 untrained participants. Participants performed an apnea at rest and following sympathetic activation using post-exercise circulatory occlusion (PECO). All apneas were performed prior to control (CON) and following vagal block using glycopyrrolate (GLY). Trained participants had lower heart rates at rest (p = 0.03) and during apneas (p = 0.009) under CON. At rest, 3 trained participants exhibited instances of junctional rhythm and 4 trained participants developed ectopy during CON apneas, whereas 3 untrained participants developed ectopic beats only with concurrent sympathetic activation (PECO). Following GLY, no arrhythmias were noted in either group. Vagal block also revealed increased cardiac chronotropy (heart rate) and inotropy (strain rate) during apnea, demonstrating a greater sympathetic influence in the absence of parasympathetic drive. Our results highlight that endurance athletes may be more susceptible to ectopy via elevated vagal tone, whereas untrained participants may only develop ectopy through autonomic conflict.

[Laparoscopic renal cryotherapy: preliminary experience]. / Crioterapia renal laparoscópica: experiencia inicial.

OBJECTIVE: Renal cryotherapy has been described as a minimally invasive procedure that represents an alternative for selected patients with small renal tumors. Our preliminary experience with this procedure is reported. MATERIAL AND METHODS: [corrected] Eighteen patients with 21 tumors with a mean tumor size of 2.2 cm (1-4) in the preoperative CT scan underwent renal cryotherapy using a double freeze-thaw cycle. The group consisted of 14 males (64%) and 4 females (18% with a mean age of 68 years (32-84). All patients had undergone prior surgery for renal tumor in the treated or the opposite kidney. A transperitoneal laparoscopic approach was used in all patients. RESULTS: Mean operating time was 196 minutes (120-140), and no patient received transfusions during or after surgery. No complications occurred in 14 patients (64%). Perirenal abscess, splenic laceration, ureteral lesion, and polar artery lesion occurred in one patient each. Peroperative biopsy was performed in 5 patients (22.7%) and was positive for renal cancer in two cases, while material was insufficient in three patients. Mean hospital stay was 6 days (2-16). Creatinine levels were 106 mg% (48-230) before surgery and 123 mg/% (52-270) 6 months after surgery. A CT scan was performed in all patients one and six months after surgery, showing a residual enhancement area in two of them. Sixteen patients (88.8%) are disease-free after a mean follow-up time of 46 months (6-116). Metastatic disease occurred in two patients (11%) in the setting of a prior renal tumor in the same or the opposite kidney and required treatment with antiangiogenic agents. CONCLUSIONS: This is the largest series reporting renal cryosurgery in Spain, in complex cases and with adequate follow-up. Results are encouraging and allow for considering renal cryotherapy among the minimally invasive procedures for nephron-sparing surgery.

Crioterapia renal laparoscópica: experiencia inicial / Laparoscopic renal cryotherapy: preliminary experience

Objetivo: La crioterapia renal se ha descrito como una técnica mínimamente invasiva que constituye una alternativa para pacientes seleccionados con tumores renales de pequeño tamaño. Presentamos nuestra experiencia preliminar con este procedimiento. Material y métodos: Dieciocho pacientes (21 tumores) con un tamaño medio de 2,2 cm (1-4) en TC prequirúrgico se trataron mediante crioterapia renal con doble ciclo de congelación. Catorce (64%) varones y 4 (18%) mujeres con una edad media de 68 años (32-84). Todos los pacientes habían tenido cirugías previas: 3 por tumor renal en el riñón que recibió el tratamiento o en el contralateral. El abordaje fue laparoscópico transperitoneal en todos los pacientes. Resultados: La media de tiempo operatorio fue de 196 min (120-420) y ningún paciente recibió transfusión intra o postoperatoria. No presentaron complicaciones 14 (64%) pacientes, y hubo un absceso perirrenal en 1 caso, laceración esplénica (1), lesión ureteral (1) y lesión de la arteria polar (1). Se realizó biopsia peroperatoria en 5 (22,7%) casos, que resultó positiva para carcinoma renal en 2 casos y material insuficiente en 3. La estancia media fue de 6 días (2-16). Los valores de creatinina preoperatorios fueron de 106 mg/% ( 48-230) y a los 6 meses de 123 mg/% (52-270). En todos los pacientes se realizó una tomografía computariza al mes y a los 6 meses de la cirugía; en 2 de ellos había una zona hipercaptante residual. Con un tiempo medio de seguimiento de 46 meses (6-116), 16 (88,8%) pacientes se encuentran libres de enfermedad. En 2 (11%) casos apareció enfermedad metastásica en el contexto de un enfermedad previa tumoral en el mismo riñón o en el contralateral, que requirió tratamiento con antiangiogénicos. Conclusiones: Se trata de la serie más amplia en nuestro país, en casos complejos y con un buen seguimiento. Los resultados son prometedores y permiten considerar la crioterapia del tumor renal dentro de las técnicas mínimamente invasivas de cirugía conservadora renal (AU)

Objective: Renal cryotherapy has been described as a minimally invasive procedure that represents an alternative for selected patients with small renal tumors. Our preliminary experience with this procedure is reported. Material y methods: Eighteen patients with 21 tumors with a mean tumor size of 2.2 cm (1-4) in the preoperative CT scan underwent renal cryotherapy using a double freeze-thaw cycle. The group consisted of 14 males (64%) and 4 females (18% with a mean age of 68 years (32-84). All patients had undergone prior surgery for renal tumor in the treated or the opposite kidney. A transperitoneal laparoscopic approach was used in all patients. Results: Mean operating time was 196 minutes (120-140), and no patient received transfusions during or after surgery. No complications occurred in 14 patients (64%). Perirenal abscess, splenic laceration, ureteral lesion, and polar artery lesion occurred in one patient each. Peroperative biopsy was performed in 5 patients (22.7%) and was positive for renal cancer in two cases, while material was insufficient in three patients. Mean hospital stay was 6 days (2‑16). Creatinine levels were 106 mg% (48-230) before surgery and 123 mg/% (52-270) 6 months after surgery. A CT scan was performed in all patients one and six months after surgery, showing a residual enhancement area in two of them. Sixteen patients (88.8%) are disease-free after a mean follow-up time of 46 months (6-116).Metastatic disease occurred in two patients (11%) in the setting of a prior renal tumor in the same or the opposite kidney and required treatmet with antiangiogenic agents. Conclusions: This is the largest series reporting renal cryosurgery in Spain, in complex cases and with adequate follow-up. Results are encouraging and allow for considering renal cryotherapy among the minimally invasive procedures for nephron-sparing surgery (AU)

Acute regulation of murine follicle-stimulating hormone beta subunit transcription by activin A.

In rodents, activins stimulate immediate-early increases in pituitary follicle-stimulating hormone beta (Fshb) subunit transcription. Here, we investigated the underlying signaling mechanisms using the mouse gonadotrope cell line, LbetaT2. Activin A increased mouse Fshb-luciferase reporter activity within 4 h through a Smad-dependent signaling pathway. The ligand rapidly stimulated formation of SMAD2/3/4 complexes that could interact with a consensus palindromic Smad binding element (SBE) in the proximal Fshb promoter. SMAD over-expression potently stimulated transcription, with the combination of SMADs 2, 3 and 4 producing the greatest synergistic activation. A mutation in the SBE that abolished Smad binding greatly impaired the effects of acute (4 h) activin A treatment and SMAD over-expression on promoter activity, but did not abolish the effects of chronic (24 h) activin A exposure. Within activated SMAD complexes, SMADs 3 and 4 appeared to bind the SBE simultaneously and the binding of both was required for maximal transcriptional activation. Interestingly, the human FSHB promoter, which lacks the consensus SBE, was neither rapidly stimulated by activin A nor by over-expressed SMADs, but was activated by 24 h activin A. Addition of the SBE to the human promoter increased both SMAD2/3/4-sensitivity and acute regulation by activin A, though not to levels observed in mouse. We postulate that short reproductive cycles in female rodents, particularly the brief interval between the primary and secondary FSH surges of the estrous cycle, require the Fshb promoter in these animals to be particularly sensitive to the rapid, Smad-dependent actions of activins on transcription. The human FSHB promoter, in contrast, is chronically regulated by activins seemingly through a SMAD-independent pathway.

Differential regulation of follicle stimulating hormone by activin A and TGFB1 in murine gonadotropes.

BACKGROUND: Activins stimulate the synthesis of follicle stimulating hormone (FSH) in pituitary gonadotropes, at least in part, by inducing transcription of its beta subunit (Fshb). Evidence from several laboratories studying transformed murine LbetaT2 gonadotropes indicates that activins signal through Smad-dependent and/or Smad-independent pathways, similar to those used by transforming growth factor beta-1 (TGFB1) in other cell types. Therefore, given common intracellular signaling mechanisms of these two ligands, we examined whether TGFBs can also induce transcription of Fshb in LbetaT2 cells as well as in purified primary murine gonadotropes. METHODS: Murine Fshb promoter-reporter (-1990/+1 mFshb-luc) activity was measured in LbetaT2 cells treated with activin A or TGFB1, and in cells transfected with either activin or TGFB receptors. The ability of the ligands to stimulate phosphorylation of Smads 2 and 3 in LbetaT2 cells was measured by western blot analysis, and expression of TGFB type I and II receptors was assessed by reverse transcriptase polymerase chain reaction in both LbetaT2 cells and primary gonadotropes purified from male mice of different ages. Finally, regulation of endogenous murine Fshb mRNA levels by activin A and TGFB1 in purified gonadotropes and whole pituitary cultures was measured using quantitative RT-PCR. RESULTS: Activin A dose-dependently stimulated -1990/+1 mFshb-luc activity in LbetaT2 cells, but TGFB1 had no effect at doses up to 5 nM. Similarly, activin A, but not TGFB1, stimulated Smad 2 and 3 phosphorylation in these cells. Constitutively active forms of the activin (Acvr1b-T206D) and TGFB (TGFBR1-T204D) type I receptors strongly stimulated -1990/+1 mFshb-luc activity, showing that mechanisms down stream of Tgfbr1 seem to be intact in LbetaT2 cells. RT-PCR analysis of LbetaT2 cells and whole adult murine pituitaries indicated that both expressed Tgfbr1 mRNA, but that Tgfbr2 was not detected in LbetaT2 cells. When cells were transfected with a human TGFBR2 expression construct, TGFB1 acquired the ability to significantly stimulate -1990/+1 mFshb-luc activity. In contrast to LbetaT2 cells, primary murine gonadotropes from young mice (8-10 weeks) contained low, but detectable levels of Tgfbr2 mRNA and these levels increased in older mice (1 yr). A second surprise was the finding that treatment of purified primary gonadotropes with TGFB1 decreased murine Fshb mRNA expression by 95% whereas activin A stimulated expression by 31-fold. CONCLUSION: These data indicate that TGFB1-insensitivity in LbetaT2 cells results from a deficiency in Tgfbr2 expression. In primary gonadotropes, however, expression of Tgfbr2 does occur, and its presence permits TGFB1 to inhibit Fshb transcription, whereas activin A stimulates it. These divergent actions of activin A and TGFB1 were unexpected and show that the two ligands may act through distinct pathways to cause opposing biological effects in primary murine gonadotropes.