Role of vitamin D in COVID-19 and other viral infections

Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.

Influence of Interrupted Childhood Biographies on Health Development: Evaluation of the Scientific Literature on the Example of Being Taken into Care*

Background: An interrupted family history, as is the case after taking someone into care, can complicate collecting family anamnesis data. In addition, the interrupted family history itself could be considered part of a person’s risk profile. Aim and methods: Literature analysis was conducted to examine whether there are scientific studies on health development after placement in out-of-home-care in order to recognise any existing medical characteristics that may be relevant for internal medical care. Results: There are few scientific publications on the health development of people after being placed in out-of-home-care. Direct reactions to the stress of being taken into custody include nausea and fever. However, effects that go beyond the acute situation and last into adulthood have also been described, such as AD(H)D, asthma, diabetes, cancer, hypertension and cardiovascular diseases (myocardial infarction, stroke), epilepsy and increased overall mortality in adulthood. Studies show that not only previous experience but also the stress of being taken into care is triggers for this. Conclusion: Information about a previous institutionalisation can hence be important for internal medical practice. The available scientific literature shows heterogeneous study methodology and no group of people with experience of out-of-home-placement has yet been scientifically accompanied for a long time period. Further studies on this could help to better weigh up the consequences of omitting and conducting an intervention for child/youth protection as well as to improve the medical care for this group of people.

Overcoming the Potential Drawbacks of Artificial Intelligence in Psychotherapy: Literature Updates

Artificial Intelligence (AI) has progressively impacted healthcare around the world. The increasing need for readily available mental health services, coupled with the swift advancement of novel technologies, prompts conversations over the viability of psychotherapy approaches using engagements with AI. Despite the positive impacts, there are recognizable drawbacks associated with the application of AI in psychotherapy. Establishing a therapeutic alliance is difficult for non-human entities. Psychotherapy is a task too complex for limited artificial intelligence. AI appears capable of handling jobs that are clearly defined and relatively straightforward. Besides, AI malfunctions, data confidentiality, informed consent, and risk of bias are potential concerns. We present a literature update of possible solutions to overcome these concerns.

Frailty in People Living with Human Immunodeficiency Virus Aged 50 Years and Older: Prevalence and Predictors

Introduction: Life expectancy improvement for people living with Human Immunodeficiency Virus (HIV) is coming up against the problems associated with aging and chronic diseases. Frailty is a concern affecting a growing number of patients, particularly the elderly in this population. Our study aimed to determine the prevalence of frailty and its predictors on people living with HIV aged 50 years and older followed at the Outpatient Treatment Clinic (CTA) in Dakar. Methodology: We conducted a cross-sectional study of descriptive and analytic purposes ranging from November 2022 to August 2023, in CTA, Dakar (Senegal). We included people living with HIV aged 50 years and older under antiretroviral therapy for at least 6 months (≥6 months). Frailty was considered according to Fried criteria with a score ≥3. To identify the predictors of frailty, we performed a multivariate logistic regression analysis using STATA software version 18. Results: We included 199 patients. The median age at the moment of the study was 58 years old [50 - 91] with a sex ratio (M/F) of 0.58. The most representative age group was that of [50 - 59] years (59.3%). HIV-1 profile was most common in 89.45%. The median duration under antiretroviral therapy was 180 months [6 - 284] and 94% of patients received a Tenofovir Disoproxil Fumarate (TDF)-containing regimen with 43% of them for at least 10 years. Viral load was undetectable (≤40 copies/ml) in 98% of cases. WHO Stage III was more common at inclusion and 55.78% had nadir TCD4+ Lymphocyte counts Conclusion: Our study confirms the high prevalence of frailty among older people living with HIV. Its prevention should consider the management of comorbidities and the implementation of non-pharmacological interventions such as nutrition.

The patients’ opinion on the use of information technologies at the Seskine Outpatient Clinic and “Centro poliklinika” Outpatient Clinic of the city of Vilnius according to the age of patients

Objectives: The objective of this study is to assess patients’ opinion of the information technologies (IT) electronic registration systems at the “Centro poliklinika” and Seskine outpatient clinics in Vilnius City. Material and Methods: The survey was conducted in May-June, 2012. In the course of the primary survey, one questionnaire was handed out to one in tenth of the newly arrived patients. Total number of 650 questionnaires was distributed. 563 respondents participated in the survey (feedback rate—86.6%). Statistical analysis of data was performed by means of personal computer using SPSS software package. Results: 54.7% of respondents state that they make use of the possibility of online registration with the family doctor. 85.05% of respondents indicate that a doctor, when making the next appointment or referring to the medical specialist, registers a patient on site by means of computer. Upon arrival of a respondent to the reception desk of the medical establishment, 90.3% of respondents are registered by means of computer. 72.4% of respondents say that they have a choice to telephone and inquire about the time of visit if they have forgotten the visit time or lost the appointment sheet. Majority of respondents using the online registration option belong to the age group between 21 and 40 years—35.3%. Conclusions: Answers by the respondents and the breakdown between “Centro poliklinika” and Seskine outpatient clinics are very similar and no essential differences have been determined.

Prevalence of high-grade HPV types among women in Astana, Kazakhstan (2018-2022)

Background:Cervical cancer is a significant public health concern worldwide,and human papillomavirus(HPV)is the leading cause of this disease.While there have been some studies on the prevalence of HPV in Kazakhstan,the country faces unique challenges in preventing and treating HPV-related diseases,including limited resources,a lack of awareness about HPV,and cultural attitudes toward sexual health.This research article aims to provide a comprehensive overview of HPV genotype distribution in Astana,Kazakhstan,for the last five years.Methods:A cross-sectional study was performed from 2018 to 2022.Study population:Kazakhstani women referring to“Olympus laboratories network”settings for HPV testing age 18-64.AmpliSens®Real-Time PCR kits for HPV genotyping 14 high-risk HPV types(16,18,31,33,35,39,45,51,52,56,58,59,66,68)were performed.Results:This study revealed the increasing trend in HR-HPV prevalence among women for five sequential year periods.As a result,approximately 43%of women referred to the HPV testing were HR-HPV positive,with the most prevalent type being HPV 16(20%),followed by HPV types 31,52,51.Conclusion:By examining the latest research on HPV and cervical cancer in Kazakhstan,we hope to contribute to developing effective public health policies and interventions to help reduce these diseases'burden in this country.Furthermore,the database will be established for future large-scale studies after vaccination implementation.

Diagnostic value ultrasound signs of stones less than or equal to 10 mm and clinicoradiological variants of ureteric colic

Objective:To determine the diagnostic value of ultrasound signs of urinary stones less than or equal to 10 mm and to determine clinico-radiological variants of ureteric colic.Methods:A total of 455 ultrasound investigations were performed in patients referring to emergency department with urolithiasis and symptoms suspected of ureteric colic between January 2021 and May 2021.In addition to microscopic evaluation of urine sediment to detect different crystals and non-contrast spiral computed tomography to detect stones,B-mode and color Doppler sonography was performed to assess the presence of acoustic shadow(AS)and twinkle artifacts(TA)as possible signs of stone(s)in ureter.Results:While the sensitivity and specificity of AS and TA were higher than 90%in patients with stones greater than 5 mm;positive prognostic values of these parameters were found to be extremely low for stones with sizes of 1-3 mm with specificity and sensitivity values not exceeding 53%.The sensitivity and specificity of AS and TA in the upper and lower ureters were higher for stones greater than or equal to 5 than for compared to those less than 5 mm.At the same time,the diagnostic values of TA and AS for middle ureter stones were very limited.The most prevalent clinico-radiological variants of ureteric colic were types I,III,and V being observed in 39%,28% and 21% cases,respectively.Conclusion:Our results demonstrate that TA and AS parameters seem to have a very low sensitivity and specificity in the diagnosis of urinary stones less than 5 mm.The diagnostic value of TA and AS increase significantly in stones greater than or equal to 5 mm.Therefore,clinicians need to be very careful for overestimating the diagnostic values of TA and AS for stones less than 5 mm and non-contrast spiral computed tomography must be the method of choice for patients presenting to emergency department with ureteric colic.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients： a pilot study

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no chromosomal aberrations were randomized into two groups： 22 received letrozole 2.5 mg per day for 6 months （Group 1：6 azoospermic＋ 16 cryptozoospermic patients）, while 24 received a placebo （Group 2：5 azoospermic＋19 cryptozoospermic patients）. The following data were collected： two semen analyses, clinical history, scrotal Duplex scans, body mass index （BMI）, Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney Utest. The relationships between sperm concentration after letrozole administration with respect to FSH, TIE2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration （medians： 400-1.290× 10^6 ml^-1; P〈0.01） and motility （medians： class A from 2% to 15%; P〈0.01）, FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to TIE2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.

Pharmacologic approaches to treatment resistant depression:Evidences and personal experience

AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.

Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

Continuous positive airway pressure to improve insulin resistance and glucose homeostasis in sleep apnea

Obstructive sleep apnea syndrome(OSAS)is a relatively common disorder in the adult population.It is associated with alterations in glucose metabolism and increases the risk for diabetes mellitus.Continuous positive airway pressure(CPAP)is the treatment of choice for OSAS.It may also have a favorable effect on insulin resistance and glucose metabolism,although relevant data is conflicting.Additional research is still needed to fully establish the effect of CPAP on glucose homeostasis.It should ascertain which patients may benefit most and how long treatment takes to induce favorable changes.Finally,patient compliance is being appreciated as a major factor influencing therapeutic outcomes,and this needs to be further examined.

Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice

Charcot osteoarthropathy (COA) is a potentially limbthreatening condition that mainly affects diabetic patients with neuropathy. In everyday practice, it presents as a red, hot, swollen foot, usually painless, and is frequently trig gered by trivial injury. Its etiology is traditionally attributed to impairment of either the autonomic nervous system, leading to increased blood flow and bone resorption, or of the peripheral nervous system, whereby loss of pain and protective sensation render the foot susceptible to repeated injury. More recently, excessive local inflammation is thought to play a decisive role. Diagnosis is based on clinical manifestation and imaging studies (plain X-rays, bone scan, Magnetic Resonance Imaging). The mainstay of management is immediate off-loading, while surgery is usually reserved for chronic cases with irreversible deformities and/or joint instability. The aim of this review is to provide an overview of COA in terms of pathogenesis, classification and clinical presentation, diagnosis and treatment, with an emphasis on the high suspicion required by clinicians for timely recognition to avoid further complications.

Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH

We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone （T） and estradiol （E2） blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels （P〈0.05 in all cases）, when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Reduction in sperm aneuploidy levels in severe oligoasthenoteratospermic patients after medical therapy： a preliminary report

The objective of this study was to investigate whether medical therapy can reduce sperm aneuploidy levels and irfiprove the results of intracytoplasmic sperm injection （ICSI） in patients with severe idiopathic oligoasthenoteratospermia （OAT）. Thirty-three infertile couples requiring ICSI because of severe idiopathic OAT after at least one unsuccessful ICSI cycle were considered. Semen parameters （concentration, motility and morphology）, the percentage of aneuploid sperm and the results of ICSI （the number of oocytes fertilized, embryos transferred, biochemical pregnancies, clinical pregnancies and live births） were compared before and after a 3-month course of treatment with L-carnitine 1 g given twice per day＋acetyI-L-carnitine 500 mg given twice per day＋one 30-mg cinnoxicam tablet every 4 days. Aneuploidy was assessed using fluorescent in situ hybridisation （FISH） performed on chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The results showed that 22 of the 33 patients had a reduced frequency of aneuploid sperm and improved sperm morphology after treatment （group 1）, and 11 showed no change （group 2）. The numbers of biochemical pregnancies, clinical pregnancies and live births were significantly higher in group I than in group 2. No significant difference was found between the groups regarding the numbers of oocytes fertilized and embryos transferred. The side effects were negligible. The numbers of ICSI pregnancies and live births in severe idiopathic OAT patients improved with a course of L-carnitine, acetyI-L-carnitine and cinnoxicam.

Y microdeletions in the Istria county,Croatia

Aim:To establish the frequency of Y chromosome microdeletions in an unselected group of infertile Croatian men. Methods:An unselected group of 105 patients (male partners of infertile couples),both with idiopathic and non- idiopathic infertility,consecutively referred to the outpatient infertility clinic,gynecology department,General Hospital Pula,Istria County,Croatia,was examined for the presence or absence of Y chromosome microdeletions by poly- merase chain reaction analysis.Results:One of the 105 men (0.95 %,95 % CI=0.17-5.2 %) was found to have a microdeletion.Conclusion:A low frequency of Y chromosome microdeletions was found in the group of unselected infertile Croatian men.

Beneficial effects of switching from β-blockers to nebivolol on the erectile function of hypertensive patients

Aim： To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods： Forty-four young and middle-aged men （31-65 years） with essential hypertension visited our outpatient clinic and took β-blocker treatment （atenolol, metoprolol or bisoprolol） for more than 6 months. All the patients completed a questionnaire regarding erectile function （International Index for Erectile Function）. Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire. Results： Twenty-nine out of the 44 （65.9%） patients who took p-blockers （atenolol, metoprolol or bisoprolol） had exhibited erectile dysfunction （ED）. Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 （69%） patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized. Conclusion： Nebivolol seems to have a beneficial effect on ED （possibly due to increased nitric oxide availability）; however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol. （Asian J Androl 2006 Mar; 8： 177-182）

Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis.METHODSA prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.RESULTSAt the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A.CONCLUSIONUndiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.

Toll-like receptor expression and signaling in human diabetic wounds

AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic patients with informed consent. Total RNA and protein were isolated and subjected to real-time polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6 mRNA expressions were increased significantly in wounds of diabetic patients compared with non-diabetic wounds(P 【 0.05). MyD88 protein expression was significantly increased in diabetic wounds compared to non-diabetic wounds. Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa B activation, and thiobarbituric acid reactive substances were increased in diabetic wounds compared to non-diabetic wounds(P 【 0.01). CONCLUSION: Collectively, our novel findings show that increased TLR expression, signaling, and activation may contribute to the hyper inflammation in the human diabetic wounds.