Localization and variable expression of G alpha(i2) in human endometrium and Fallopian tubes

BACKGROUND: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit G alpha(i2) in the human endometrium and Fallopian tube and changes in G alpha(i2) expression in human endometrium during the menstrual cycle. METHODS: The expression of G alpha(i2) was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining. Cyclic changes in G alpha(i2) expression during the menstrual cycle were evaluated by quantitative real-time PCR. RESULTS: We found G alpha(i2) to be expressed in human endometrium, Fallopian tube tissue and in primary cultures of Fallopian tube epithelial cells. Our studies revealed enriched localization of G alpha(i2) in Fallopian tube cilia and in endometrial glands. We showed that G alpha(i2) expression in human endometrium changes significantly during the menstrual cycle, with a higher level in the secretory versus proliferative and menstrual phases (P < 0.05). CONCLUSIONS: G alpha(i2) is specifically localized in human Fallopian tube epithelial cells, particularly in the cilia, and is likely to have a cilia-specific role in reproduction. Significantly variable expression of G alpha(i2) during the menstrual cycle suggests G alpha(i2) might be under hormonal regulation in the female reproductive tract in vivo.     

Clinical and economic burden of wound care in the tropics: a 5‐year institutional population health review

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5‐year institutional population health review. Within our data analysis, wounds are broadly classified into neuro‐ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound‐related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound‐related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1‐year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years‐old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1‐year all‐cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound‐related 30‐day re‐admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789–17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.     

A randomised trial comparing conventional semen parameters,sperm DNA fragmentation levels and satisfaction levels between semen collection at home and at the clinic

The aim of the randomised trial was to compare conventional semen parameters, sperm DNA fragmentation levels and satisfaction levels between semen samples collected at home and at the clinic. We recruited 110 men with a history of infertility for at least 1 year from the outpatient andrology clinic. Each man collected two semen samples, one at home and one at the clinic. Men were randomly assigned into the home first (n = 55) or clinic first (n = 55) groups. The primary outcome was sperm concentration. There was no significant difference in sperm concentration, sperm DNA fragmentation levels or other conventional semen parameters between home first and clinic first samples (p > .05), while satisfaction levels were significantly higher for home first samples (p < .01). Consistent results were obtained when comparing home-collected and clinic-collected samples within individuals. Men can be offered the option to collect semen samples at home for examination or assisted reproduction without compromising semen quality, especially for those with difficulty in producing semen samples at the clinic.     

Evaluating the safety and efficacy of the 1,440‐nm laser in the treatment of photodamage in Asian skin

Background and Objective

As the demand for diminished procedure‐associated downtime continues to increase, nonablative fractional laser resurfacing is becoming a more popular intervention in the progression of photoaging. Patients with pigmented skin and a mild degree of photodamage may be particularly suited for a less intensive laser treatment. In this study, we have evaluated the safety and efficacy of a low energy, low density 1,440‐nm fractional laser in the treatment of multiple signs of photoaging including dyspigmentation, wrinkling, tissue laxity, enlarged pores, and skin roughness in Asians.

Study Design/Materials and Methods

Ten Chinese subjects with Fitzpatrick skin types III–V and visible signs of photodamage participated in this study. Patients received four treatments at 2‐week intervals with a 1,440‐nm diode‐based fractional laser. Photographs were taken at baseline, 2 weeks after each of the first three treatments and 4 weeks after the final treatment. Images were evaluated independently by two physicians. Clinical improvement and adverse events were analyzed. Discomfort, heat sensation and overall patient satisfaction associated with the procedure were also quantified.

Results

In this prospective single‐arm study, signs of photoaging were examined after treatment with the 1,440‐nm laser. Here we show that a series of four treatments with this device produced a mild improvement in skin texture, pigmentation, and wrinkling. Changes in pore size and skin laxity failed to reach statistical significance. Immediate after‐effects of the procedure included erythema and edema which were transient and left no permanent sequela. A significant proportion of patients reported some degree of discomfort during the procedure despite use of a topical anesthetic. One patient developed a discrete, localized area of post‐inflammatory hyperpigmentation which completely resolved by the final follow up visit.

Conclusion

The low energy, low density nonablative 1,440‐nm fractional laser produces a mild improvement in select signs of photodamage after four treatments without any long‐term adverse effects. Lasers Surg. Med. 46:375–379, 2014. © 2014 Wiley Periodicals, Inc.     

Proton Therapy for Skull Base Chordomas: An Outcome Study from the University of Florida Proton Therapy Institute

Objectives Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the conformal advantage of delivering a high postoperative dose to the tumor bed. We present our experience using proton therapy to treat 33 patients with skull base chordomas. Design Retrospective outcomes study. Setting University of Florida Proton Therapy Institute; 2007 to 2011. Participants A total of 33 patients with skull base chordomas received postoperative three-dimensional conformal proton therapy. The patients were 79% male and 6% diabetic; 27% had received a gross total resection. Main Outcome Measures The gross tumor/tumor bed received a dose between 77.4 CGE and 79.4 CGE. Local control and overall survival were tracked, and radiation toxicity was assessed using a modified Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme. Results Median follow-up for all patients was 21 months. Local control and overall survival rates at 2 years were 86% and 92%, respectively. Grade 2 toxicity was observed in 18% of our cohort in the form of unilateral hearing loss partially corrected with a hearing aid. No grade 2 or higher optic or brainstem toxicities were observed. Conclusions Proton therapy is an effective treatment modality for skull base chordomas.     

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study)

Background

The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen.

Objective:

To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting.

Methods:

A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed.

Results:

Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of “red man syndrome”, and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400.

Conclusion:

The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.     

Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis

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